A Primer on the Genetics of Comorbid Eating Disorders and Substance Use Disorders.

PubMed

Munn-Chernoff, Melissa A; Baker, Jessica H

2016-03-01

Eating disorders (EDs) and substance use disorders (SUDs) frequently co-occur; however, the reasons for this are unclear. We review the current literature on genetic risk for EDs and SUDs, as well as preliminary findings exploring whether these classes of disorders have overlapping genetic risk. Overall, genetic factors contribute to individual differences in liability to multiple EDs and SUDs. Although initial family studies concluded that no shared familial (which includes genetic) risk between EDs and SUDs exists, twin studies suggest a moderate proportion of shared variance is attributable to overlapping genetic factors, particularly for those EDs characterized by binge eating and/or inappropriate compensatory behaviours. No adoption or molecular genetic studies have examined shared genetic risk between these classes of disorders. Research investigating binge eating and inappropriate compensatory behaviours using emerging statistical genetic methods, as well as examining gene-environment interplay, will provide important clues into the aetiology of comorbid EDs and SUDs. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Cross-Cultural Comparison of Genetic and Cultural Transmission of Smoking Initiation Using an Extended Twin Kinship Model.

PubMed

Maes, Hermine H; Morley, Kate; Neale, Michael C; Kendler, Kenneth S; Heath, Andrew C; Eaves, Lindon J; Martin, Nicholas G

2018-06-01

Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime 'ever' smoking measure was obtained from twins and relatives in the 'Virginia 30,000' sample and the 'Australian 25,000'. Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI.

Genetic and Environmental Influences on Disability Pension Due To Mental Diagnoses: Limited Importance of Major Depression, Generalized Anxiety, and Chronic Fatigue.

PubMed

Narusyte, Jurgita; Ropponen, Annina; Alexanderson, Kristina; Svedberg, Pia

2016-02-01

Previous research indicates that liability to disability pension (DP) due to mental diagnoses is moderately influenced by genetic factors. This study investigates whether genetic contributions to the liability to DP due to mood and neurotic diagnoses overlap with the genetic influences on major depression (MD), generalized anxiety disorder (GAD), or chronic fatigue (CF). A prospective cohort study including 9,985 female twins born in Sweden 1933-1958. The presence of MD, GAD, and CF was assessed by computer-assisted telephone interviews conducted in 1998-2002. Data on DP due to mood and neurotic diagnoses were obtained from nationwide registers for the years 1998-2010. Common genetic and environmental influences on the phenotypes were estimated by applying structural equation modeling. The prevalence of MD/GAD was 30%, CF 8%, and DP due to mood and neurotic diagnoses 3% in 2010. Genetic effects on MD/GAD explained 31% of the total genetic variation in DP, whereas genetic contributions in common with CF were small and not significant. The majority of the total non-shared environmental variance in DP (85%) was explained by the factors that were unique to DP. Large proportions of genetic and non-shared environmental influences in DP due to mood and neurotic diagnoses were not explained by the contributions from MD/GAD or CF. The results suggest that the process leading to DP is complex and influenced by factors other than those related to the disorder underlying DP.

Personality disorder traits, family environment, and alcohol misuse: a multivariate behavioural genetic analysis.

PubMed

Jang, K L; Vernon, P A; Livesley, W J

2000-06-01

This study seeks to estimate the extent to which a common genetic and environmental basis is shared between (i) traits delineating specific aspects of antisocial personality and alcohol misuse, and (ii) childhood family environments, traits delineating broad domains of personality pathology and alcohol misuse. Postal survey data were collected from monozygotic and dizygotic twin pairs. Twin pairs were recruited from Vancouver, British Columbia and London, Ontario, Canada using newspaper advertisements, media stories and twin clubs. Data obtained from 324 monozygotic and 335 dizygotic twin pairs were used to estimate the extent to which traits delineating specific antisocial personality traits and alcohol misuse shared a common genetic and environmental aetiology. Data from 81 monozygotic and 74 dizygotic twin pairs were used to estimate the degree to which traits delineating personality pathology, childhood family environment and alcohol misuse shared a common aetiology. Current alcohol misuse and personality pathology were measured using scales contained in the self-report Dimensional Assessment of Personality Pathology. Perceptions of childhood family environment were measured using the self-report Family Environment Scale. Multivariate genetic analyses showed that a subset of traits delineating components of antisocial personality (i.e. grandiosity, attention-seeking, failure to adopt social norms, interpersonal violence and juvenile antisocial behaviours) are influenced by genetic factors in common to alcohol misuse. Genetically based perceptions of childhood family environment had little relationship with alcohol misuse. Heritable personality factors that influence the perception of childhood family environment play only a small role in the liability to alcohol misuse. Instead, liability to alcohol misuse is related to genetic factors common a specific subset of antisocial personality traits describing conduct problems, narcissistic and stimulus-seeking behaviour.

Extending the ‘cross-disorder’ relevance of executive functions to dimensional neuropsychiatric traits in youth

PubMed Central

McGrath, Lauren M.; Braaten, Ellen B.; Doty, Nathan D.; Willoughby, Brian L.; Wilson, H. Kent; O’Donnell, Ellen H.; Colvin, Mary K.; Ditmars, Hillary L.; Blais, Jessica E.; Hill, Erin N.; Metzger, Aaron; Perlis, Roy H.; Willcutt, Erik G.; Smoller, Jordan W.; Waldman, Irwin D.; Faraone, Stephen V.; Seidman, Larry J.; Doyle, Alysa E.

2016-01-01

Background Evidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with ‘cross-disorder’ relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability. Methods Data are from 393 participants, ages 8 to 17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of autism spectrum disorder, bipolar illness and schizophrenia, including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively. Results We modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting it related to a general increase in psychopathology symptoms across those dimensions. Conclusions Findings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relate to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability. PMID:26411927

Mechanisms underlying the lifetime co-occurrence of tobacco and cannabis use in adolescent and young adult twins

PubMed Central

Agrawal, Arpana; Silberg, Judy L.; Lynskey, Michael T.; Maes, Hermine H.; Eaves, Lindon J.

2009-01-01

Using twins assessed during adolescence (Virginia Twin Study of Adolescent Behavioral Development: 8–17 years) and followed up in early adulthood (Young Adult Follow-Up, 18–27 years), we tested 13 genetically informative models of co-occurrence, adapted for the inclusion of covariates. Models were fit, in Mx, to data at both assessments allowing for a comparison of the mechanisms that underlie the lifetime co-occurrence of cannabis and tobacco use in adolescence and early adulthood. Both cannabis and tobacco use were influenced by additive genetic (38–81%) and non-shared environmental factors with the possible role of non-shared environment in the adolescent assessment only. Causation models, where liability to use cannabis exerted a causal influence on the liability to use tobacco fit the adolescent data best, while the reverse causation model (tobacco causes cannabis) fit the early adult data best. Both causation models (cannabis to tobacco and tobacco to cannabis) and the correlated liabilities model fit data from the adolescent and young adult assessments well. Genetic correlations (0.59–0.74) were moderate. Therefore, the relationship between cannabis and tobacco use is fairly similar during adolescence and early adulthood with reciprocal influences across the two psychoactive substances. However, our study could not exclude the possibility that ‘gateways’ and ‘reverse gateways’, particularly within a genetic context, exist, such that predisposition to using one substance (cannabis or tobacco) modifies predisposition to using the other. Given the high addictive potential of nicotine and the ubiquitous nature of cannabis use, this is a public health concern worthy of considerable attention. PMID:20047801

A sibling based design to quantify genetic and shared environmental effects of venous thromboembolism in Sweden.

PubMed

Zöller, Bengt; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina

2017-01-01

Few large studies have examined the heritability of venous thromboembolism (VTE). Moreover, twin studies have been suggested to overestimate heritability. The aim of the present study was to determine the heritability nationwide in the general Swedish population using full siblings and half-siblings. VTE was defined using the Swedish patient register. Full sibling (FS) and half-sibling (HS) pairs born 1950-1990 were obtained from the Swedish Multi-generation Register. A maximum of 5years age difference was allowed. We also required that the individuals within the pair should reside in the same household for at least 8years or not at all (0years) before the youngest turned 16. Information about sibling pair residence within the same household, small residential area, and municipality was obtained from Statistics Sweden. We assumed three potential sources of liability to VTE: additive genetic (A), shared (or common/familial) environment (C), and unique environment (E) components. Totally 881,206 FS pairs and 95,198 HS pairs were included. The full model predicted heritability for VTE with 47% for males and 40% for females. Environmental factors shared by siblings contributed to 0% of the variance in liability for both sexes, and unique environment (E) components accounted for 53% in males and 60% in females. The high heritability of VTE risk indicates that genetic susceptibility plays a substantial role for VTE in the Swedish general population. Overestimation of heritability from twin studies is not likely. The proportion of the variance attributable to shared familial environment factors is small. Subject codes: Genetics, epidemiology, thrombosis, cardiovascular disease, embolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aetiology of teenage childbearing: reasons for familial effects.

PubMed

Olausson, P O; Lichtenstein, P; Cnattingius, S

2000-03-01

The aims of the present study were to evaluate the contribution of the genetic and environmental factors to the risk of teenage childbearing, and to study whether life style, socio-economic conditions, and personality traits could explain possible familial effects. We linked two population-based registers: the Swedish Twin Register and the Swedish Medical Birth Register. The study covers female twin pairs born between 1953 and 1958, having their first infant before the age of 30 years (n = 1885). In order to separate familial effects from other environmental influences, and genetic effects from shared environmental effects, only complete twin pairs with known zygosity were included, in all 260 monozygotic and 370 dizygotic twin pairs. We used quantitative genetic analyses to evaluate the importance of genetic and environmental effects for liability to teenage childbearing. Logistic regression analyses were used to estimate the effects of life style, socio-economic situation, and personality on the probability of teenage childbearing, and to study whether psychosocial factors could explain possible familial effects. Fifty-nine percent (0-76%) of the variance in being a teenage mother was attributable to heritable factors; 0% (0-49%) was due to shared environmental factors; and 41% (23-67%) was explained by non-shared environmental factors. Thus, the data were consistent with the hypothesis that the familial aggregation of teenage childbearing is completely explained by genetic factors, although the alternative hypothesis that familial aggregation is entirely explained by shared environmental factors cannot be ruled out. Significant effects of smoking habits, housing conditions, and educational level were found in relation to liability to teenage childbearing. However, the familial effects on risk of teenage childbearing were not mediated through similarities in life style and socio-economic factors. When studying risk factors for teenage childbearing, it is recommended to include life style and socio-economic variables as well as information about family history of teenage childbearing. Twin Research (2000) 3, 23-27.

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

PubMed

Blokland, Gabriëlla A M; Mesholam-Gately, Raquelle I; Toulopoulou, Timothea; Del Re, Elisabetta C; Lam, Max; DeLisi, Lynn E; Donohoe, Gary; Walters, James T R; Seidman, Larry J; Petryshen, Tracey L

2017-07-01

Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comorbidity of depression with levels of smoking: an exploration of the shared familial risk hypothesis.

PubMed

Johnson, Eric O; Rhee, Soo Hyun; Chase, Gary A; Breslau, Naomi

2004-12-01

Comorbidity of depression and smoking is well recognized, but results from studies that have assessed alternative explanations have varied by the level of smoking and the study method. We examined all 13 etiology models of comorbidity described by Neale and Kendler (American Journal of Genetics, 57, 935-953, 1995) for depression and each of four levels of smoking to shed light on the role that differing definitions might have played in generating the conflicting findings. Data came from 979 young adults aged 26-35 years who participated in an epidemiological cohort study in southeastern Michigan. Respondent and family history data on parental smoking and depression were analyzed using the biometric modeling method for family data, which Rhee and colleagues (Journal of Child Psychology and Psychiatry and Allied Disciplines, 44, 612-636, 2003; Behavior Genetics, 34, 251-265, 2004) have shown to be valid more frequently than traditional prevalence analyses. Results of the biometric model fitting suggested that for ever smoking, the comorbidity with depression may be related to chance or a high liability threshold for smoking only. In contrast, a correlated liabilities model fit the data best for the comorbidity of depression with daily, heavy, and nicotine-dependent smoking. The familial correlations accounted for 73%-95% of the total variance shared between depression and these levels of smoking. These results differ from analyses of these data using a traditional prevalence approach, which found no evidence of shared familial liability. The conflicting findings of the studies that have examined the relationship between smoking and depression may be attributable to differences in definition of the disorders and the methods used to analyze them.

Shared Genetics and Couple-Associated Environment Are Major Contributors to the Risk of Both Clinical and Self-Declared Depression.

PubMed

Zeng, Yanni; Navarro, Pau; Xia, Charley; Amador, Carmen; Fernandez-Pujals, Ana M; Thomson, Pippa A; Campbell, Archie; Nagy, Reka; Clarke, Toni-Kim; Hafferty, Jonathan D; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2016-12-01

Both genetic and environmental factors contribute to risk of depression, but estimates of their relative contributions are limited. Commonalities between clinically-assessed major depressive disorder (MDD) and self-declared depression (SDD) are also unclear. Using data from a large Scottish family-based cohort (GS:SFHS, N=19,994), we estimated the genetic and environmental variance components for MDD and SDD. The components representing the genetic effect associated with genome-wide common genetic variants (SNP heritability), the additional pedigree-associated genetic effect and non-genetic effects associated with common environments were estimated in a linear mixed model (LMM). Both MDD and SDD had significant contributions from components representing the effect from common genetic variants, the additional genetic effect associated with the pedigree and the common environmental effect shared by couples. The estimate of correlation between SDD and MDD was high (r=1.00, se=0.20) for common-variant-associated genetic effect and lower for the additional genetic effect from the pedigree (r=0.57, se=0.08) and the couple-shared environmental effect (r=0.53, se=0.22). Both genetics and couple-shared environmental effects were major factors influencing liability to depression. SDD may provide a scalable alternative to MDD in studies seeking to identify common risk variants. Rarer variants and environmental effects may however differ substantially according to different definitions of depression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Sexual offending runs in families: A 37-year nationwide study.

PubMed

Långström, Niklas; Babchishin, Kelly M; Fazel, Seena; Lichtenstein, Paul; Frisell, Thomas

2015-04-01

Sexual crime is an important public health concern. The possible causes of sexual aggression, however, remain uncertain. We examined familial aggregation and the contribution of genetic and environmental factors to sexual crime by linking longitudinal, nationwide Swedish crime and multigenerational family registers. We included all men convicted of any sexual offence (N = 21,566), specifically rape of an adult (N = 6131) and child molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and brothers of sexual offenders were compared with corresponding rates in fathers and brothers of age-matched population control men without sexual crime convictions. We also modelled the relative influence of genetic and environmental factors to the liability of sexual offending. We found strong familial aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 4.5-5.9] among full brothers of convicted sexual offenders. Familial aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2-4.4) among paternal half-brothers (OR = 2.1, 95% CI = 1.5-2.9) and maternal half-brothers (OR = 1.7, 95% CI = 1.2-2.4). Statistical modelling of the strength and patterns of familial aggregation suggested that genetic factors (40%) and non-shared environmental factors (58%) explained the liability to offend sexually more than shared environmental influences (2%). Further, genetic effects tended to be weaker for rape of an adult (19%) than for child molestation (46%). We report strong evidence of familial clustering of sexual offending, primarily accounted for by genes rather than shared environmental influences. Future research should possibly test the effectiveness of selective prevention efforts for male first-degree relatives of sexually aggressive individuals, and consider familial risk in sexual violence risk assessment.

IQ and schizophrenia in a Swedish national sample: their causal relationship and the interaction of IQ with genetic risk.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina

2015-03-01

The authors sought to clarify the relationship between IQ and subsequent risk for schizophrenia. IQ was assessed at ages 18-20 in 1,204,983 Swedish males born between 1951 and 1975. Schizophrenia was assessed by hospital diagnosis through 2010. Cox proportional hazards models were used to investigate future risk for schizophrenia in individuals as a function of their IQ score, and then stratified models using pairs of relatives were used to adjust for familial cluster. Finally, regression models were used to examine the interaction between IQ and genetic liability on risk for schizophrenia. IQ had a monotonic relationship with schizophrenia risk across the IQ range, with a mean increase in risk of 3.8% per 1-point decrease in IQ; this association was stronger in the lower than the higher IQ range. Co-relative control analyses showed a similar association between IQ and schizophrenia in the general population and in cousin, half-sibling, and full-sibling pairs. A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low than high intelligence. The IQ-genetic liability interaction arose largely from IQ differences between close relatives. IQ assessed in late adolescence is a robust risk factor for subsequent onset of schizophrenia. This association is not the result of a declining IQ associated with insidious onset. In this large, representative sample, we found no evidence for a link between genius and schizophrenia. Co-relative control analyses showed that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. The strongest effect was seen with IQ differences within families. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia.

A behavioral-genetic investigation of bulimia nervosa and its relationship with alcohol use disorder

PubMed Central

Trace, Sara Elizabeth; Thornton, Laura Marie; Baker, Jessica Helen; Root, Tammy Lynn; Janson, Lauren Elizabeth; Lichtenstein, Paul; Pedersen, Nancy Lee; Bulik, Cynthia Marie

2013-01-01

Bulimia nervosa (BN) and alcohol use disorder (AUD) frequently co-occur and may share genetic factors; however, the nature of their association is not fully understood. We assessed the extent to which the same genetic and environmental factors contribute to liability to BN and AUD. A bivariate structural equation model using a Cholesky decomposition was fit to data from 7,241 women who participated in the Swedish Twin study of Adults: Genes and Environment. The proportion of variance accounted for by genetic and environmental factors for BN and AUD and the genetic and environmental correlations between these disorders were estimated. In the best-fitting model, the heritability estimates were 0.55 (95% CI: 0.37; 0.70) for BN and 0.62 (95% CI: 0.54; 0.70) for AUD. Unique environmental factors accounted for the remainder of variance for BN. The genetic correlation between BN and AUD was 0.23 (95% CI: 0.01; 0.44), and the correlation between the unique environmental factors for the two disorders was 0.35 (95% CI: 0.08; 0.61), suggesting moderate overlap in these factors. Findings from this investigation provide additional support that some of the same genetic factors may influence liability to both BN and AUD. PMID:23790978

A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Maes, Hermine H; Sundquist, Kristina; Lichtenstein, Paul; Sundquist, Jan

2015-04-01

Prior studies, utilizing interview-based assessments, suggest that most of the genetic risk factors for drug abuse (DA) are non-specific with a minority acting specifically on risk for abuse of particular psychoactive substance classes. We seek to replicate these findings using objective national registry data. We examined abuse of cannabis, stimulants (including cocaine) and sedatives ascertained from national Swedish registers in male-male monozygotic (1720 pairs) and dizygotic twins (1219 pairs) combined with near-age full siblings (76,457 pairs) to provide sufficient power. Modeling was performed using Mx. A common pathway model fitted better than an independent pathway model. The latent liability to DA was highly heritable but also influenced by shared environment. Cannabis, stimulant and sedative abuse all loaded strongly on the common factor. Estimates for the total heritability for the three forms of substance abuse ranged from 64 to 70%. Between 75 and 90% of that genetic risk was non-specific, coming from the common factor with the remainder deriving from substance specific genetic risk factors. By contrast, all of the shared environmental effects, which accounted for 18-20% of the variance in liability, were non-specific. In accord with prior studies based on personal interviews, the large preponderance of genetic risk factors for abuse of specific classes of psychoactive substance are non-specific. These results suggest that genetic variation in the primary sites of action of the psychoactive drugs, which differ widely across most drug classes, play a minor role in human individual differences in risk for DA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chronic Fatigue and Personality: A Twin Study of Causal Pathways and Shared Liabilities

PubMed Central

Poeschla, Brian; Strachan, Eric; Dansie, Elizabeth; Buchwald, Dedra S.; Afari, Niloofar

2013-01-01

Background The etiology of chronic fatigue syndrome (CFS) remains unknown. Personality traits influence well-being and may play a role in CFS and unexplained chronic fatigue. Purpose To examine the association of emotional instability and extraversion with chronic fatigue and CFS in a genetically informative sample. Methods We evaluated 245 twin pairs for two definitions of chronic fatigue. They completed the Neuroticism and Extraversion subscales of the NEO-FFI. Using a co-twin control design, we examined the association between personality and chronic fatigue. Results Higher emotional instability was associated with both definitions of chronic fatigue and was confounded by shared genetics. Lower extraversion was also associated with both definitions of fatigue, but was not confounded by familial factors. Conclusions Both emotional instability and extraversion are related to chronic fatigue and CFS. Whereas emotional instability and chronic fatigue are linked by shared genetic mechanisms, the relationship with extraversion may be causal and bi-directional. PMID:23361410

The structure of genetic and environmental risk factors for phobias in women.

PubMed

Czajkowski, N; Kendler, K S; Tambs, K; Røysamb, E; Reichborn-Kjennerud, T

2011-09-01

To explore the genetic and environmental factors underlying the co-occurrence of lifetime diagnoses of DSM-IV phobia. Female twins (n=1430) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime specific phobia, social phobia and agoraphobia. Comorbidity between the phobias were assessed by odds ratios (ORs) and polychoric correlations and multivariate twin models were fitted in Mx. Phenotypic correlations of lifetime phobia diagnoses ranged from 0.55 (agoraphobia and social phobia, OR 10.95) to 0.06 (animal phobia and social phobia, OR 1.21). In the best fitting twin model, which did not include shared environmental factors, heritability estimates for the phobias ranged from 0.43 to 0.63. Comorbidity between the phobias was accounted for by two common liability factors. The first loaded principally on animal phobia and did not influence the complex phobias (agoraphobia and social phobia). The second liability factor strongly influenced the complex phobias, but also loaded weak to moderate on all the other phobias. Blood phobia was mainly influenced by a specific genetic factor, which accounted for 51% of the total and 81% of the genetic variance. Phobias are highly co-morbid and heritable. Our results suggest that the co-morbidity between phobias is best explained by two distinct liability factors rather than a single factor, as has been assumed in most previous multivariate twin analyses. One of these factors was specific to the simple phobias, while the other was more general. Blood phobia was mainly influenced by disorder specific genetic factors.

The structure of genetic and environmental risk factors for phobias in women

PubMed Central

Czajkowski, N.; Kendler, K. S.; Tambs, K.; Røysamb, E.; Reichborn-Kjennerud, T.

2011-01-01

Background To explore the genetic and environmental factors underlying the co-occurrence of lifetime diagnoses of DSM-IV phobia. Method Female twins (n = 1430) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime specific phobia, social phobia and agoraphobia. Comorbidity between the phobias were assessed by odds ratios (ORs) and polychoric correlations and multivariate twin models were fitted in Mx. Results Phenotypic correlations of lifetime phobia diagnoses ranged from 0.55 (agoraphobia and social phobia, OR 10.95) to 0.06 (animal phobia and social phobia, OR 1.21). In the best fitting twin model, which did not include shared environmental factors, heritability estimates for the phobias ranged from 0.43 to 0.63. Comorbidity between the phobias was accounted for by two common liability factors. The first loaded principally on animal phobia and did not influence the complex phobias (agoraphobia and social phobia). The second liability factor strongly influenced the complex phobias, but also loaded weak to moderate on all the other phobias. Blood phobia was mainly influenced by a specific genetic factor, which accounted for 51% of the total and 81% of the genetic variance. Conclusions Phobias are highly co-morbid and heritable. Our results suggest that the co-morbidity between phobias is best explained by two distinct liability factors rather than a single factor, as has been assumed in most previous multivariate twin analyses. One of these factors was specific to the simple phobias, while the other was more general. Blood phobia was mainly influenced by disorder specific genetic factors. PMID:21211096

31 CFR 50.92 - Determination of pro rata share.

Code of Federal Regulations, 2010 CFR

2010-07-01

... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... providing property and casualty insurance under the Program if there were no cap on annual liability under... estimates that aggregate insured losses may exceed the cap on annual liability for a Program Year, then...

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

PubMed

Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Geschwind, Daniel H; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian L; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K; Klauck, Sabine M; Klei, Lambertus; Knowles, James A; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lee, Phil H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nurnberger, John I; Nwulia, Evaristus A; Nyholt, Dale R; O'Dushlaine, Colm; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael J; Palotie, Aarno; Parr, Jeremy R; Paterson, Andrew D; Pato, Carlos N; Pato, Michele T; Penninx, Brenda W; Pergadia, Michele L; Pericak-Vance, Margaret A; Pickard, Benjamin S; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J; Quinn, Emma M; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R; Sanders, Stephan J; Santangelo, Susan L; Sergeant, Joseph A; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F; Scheftner, William A; Schellenberg, Gerard D; Scherer, Stephen W; Schork, Nicholas J; Schulze, Thomas G; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J; Shi, Jianxin; Shilling, Paul D; Shyn, Stanley I; Silverman, Jeremy M; Slager, Susan L; Smalley, Susan L; Smit, Johannes H; Smith, Erin N; Sonuga-Barke, Edmund J S; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S; Strohmaier, Jana; Stroup, T Scott; Sutcliffe, James S; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C; Todorov, Alexandre A; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M; Vieland, Veronica J; Vincent, John B; Visscher, Peter M; Walsh, Christopher A; Wassink, Thomas H; Watson, Stanley J; Weissman, Myrna M; Werge, Thomas; Wienker, Thomas F; Wijsman, Ellen M; Willemsen, Gonneke; Williams, Nigel; Willsey, A Jeremy; Witt, Stephanie H; Xu, Wei; Young, Allan H; Yu, Timothy W; Zammit, Stanley; Zandi, Peter P; Zhang, Peng; Zitman, Frans G; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R; Sklar, Pamela; Daly, Mark J; O'Donovan, Michael C; Craddock, Nicholas; Sullivan, Patrick F; Smoller, Jordan W; Kendler, Kenneth S; Wray, Naomi R

2013-09-01

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Sharing of track by transit and freight railroads : liability and insurance issues

DOT National Transportation Integrated Search

2005-09-21

This report explores the issues of liability and insurance that arise in planning and operating track shared between light rail transit and freight railroads. Shared track operations involve some unique risks, and insurance is used to mitigate or man...

IQ and Schizophrenia in a Swedish National Sample: Their Causal Relationship and the Interaction of IQ with Genetic Risk

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina

2015-01-01

Objective To clarify the relationship between IQ and subsequent risk for schizophrenia. Method IQ was assessed at ages 18-20 in 1,204,983 Swedish males born 1951-1975. Schizophrenia was assessed by hospital diagnosis through 2010. Results IQ had a monotonic relationship with schizophrenia risk across the IQ range with a mean change of 3.8% in risk per IQ point. This association, stronger in the lower versus higher IQ range, was similar if onsets within five years of testing were censored. No increased risk for schizophrenia was seen in those with highest intelligence. Co-relative control analyses showed a similar IQ-schizophrenia association in the general population and in cousin, half-sibling and full-sibling pairs. A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low versus high intelligence. The IQ-genetic liability interaction arose largely from IQ differences between close relatives. Conclusions IQ assessed in late adolescence is a robust risk factor for subsequent onset of schizophrenia. This association is not the result of a declining IQ associated with insidious onset. In this large, representative sample, we found no evidence for a link between genius and schizophrenia. Co-relative control analyses show that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. The strongest effect was seen with IQ differences within families. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia. PMID:25727538

Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees.

PubMed

Campbell, Desmond D; Li, Yiming; Sham, Pak C

2018-03-01

Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported methodology based on a liability-threshold model. Multifactorial disease models incorporating all the following features in combination are handled: quantitative risk factors (including polygenic scores), categorical risk factors (including major genetic risk loci), stratified age of onset curves, and the partition of the population variance in disease liability into genetic, shared, and unique environment effects. It allows the application of such models to disease pedigrees. Pedigree-related outputs are (i) individual disease risk for pedigree members, (ii) n year risk for unaffected pedigree members, and (iii) the disease pedigree's joint liability distribution. Risk prediction for each pedigree member is based on using the constructed disease model to appropriately weigh evidence on disease risk available from personal attributes and family history. Evidence is used to construct the disease pedigree's joint liability distribution. From this, lifetime and n year risk can be predicted. Example disease models and pedigrees are provided at the website and are used in accompanying tutorials to illustrate the features available. The website is built on an R package which provides the functionality for pedigree validation, disease model construction, and risk prediction. Website: http://grass.cgs.hku.hk:3838/mdrc/current. © 2017 WILEY PERIODICALS, INC.

Sexual offending runs in families: A 37-year nationwide study

PubMed Central

Långström, Niklas; Babchishin, Kelly M; Fazel, Seena; Lichtenstein, Paul; Frisell, Thomas

2015-01-01

Background: Sexual crime is an important public health concern. The possible causes of sexual aggression, however, remain uncertain. Methods: We examined familial aggregation and the contribution of genetic and environmental factors to sexual crime by linking longitudinal, nationwide Swedish crime and multigenerational family registers. We included all men convicted of any sexual offence (N = 21 566), specifically rape of an adult (N = 6131) and child molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and brothers of sexual offenders were compared with corresponding rates in fathers and brothers of age-matched population control men without sexual crime convictions. We also modelled the relative influence of genetic and environmental factors to the liability of sexual offending. Results: We found strong familial aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 4.5–5.9] among full brothers of convicted sexual offenders. Familial aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2–4.4) among paternal half-brothers (OR = 2.1, 95% CI = 1.5–2.9) and maternal half-brothers (OR = 1.7, 95% CI = 1.2–2.4). Statistical modelling of the strength and patterns of familial aggregation suggested that genetic factors (40%) and non-shared environmental factors (58%) explained the liability to offend sexually more than shared environmental influences (2%). Further, genetic effects tended to be weaker for rape of an adult (19%) than for child molestation (46%). Conclusions: We report strong evidence of familial clustering of sexual offending, primarily accounted for by genes rather than shared environmental influences. Future research should possibly test the effectiveness of selective prevention efforts for male first-degree relatives of sexually aggressive individuals, and consider familial risk in sexual violence risk assessment. PMID:25855722

Clinical multiple sclerosis occurs at one end of a spectrum of CNS pathology: a modified threshold liability model leads to new ways of thinking about the cause of clinical multiple sclerosis.

PubMed

Haegert, David G

2005-01-01

Multiple sclerosis (MS) is a complex trait, the causes of which are elusive. A threshold liability model influences thinking about the causes of this disorder. According to this model, a population has a normal distribution of genetic liability to MS. In addition, a threshold exists, so that MS begins when an individual's liability exceeds the MS threshold; environmental and other causative factors may increase or decrease an individual's MS liability. It is argued here, however, that this model is misleading, as it is based on the incorrect assumption that MS is a disorder that one either has or does not have. This paper hypothesizes, instead, that patients with a diagnosis of MS share identical CNS pathology, termed MS pathology, with some individuals who have a diagnosis of possible MS and with some apparently healthy individuals, who may never have a diagnosis of MS. In order to accommodate this hypothesis, the current threshold liability model is modified as follows. (1) In addition to a normal distribution of MS liability within a population, a spectrum of MS pathology occurs in some who have a high MS liability. (2) A clinical MS threshold exists at a point on this liability distribution, where the burden and distribution of MS pathology permits a diagnosis of clinical MS. (3) Additional thresholds exist that correspond to a lower MS liability and a lesser burden of MS pathology than occur at the clinical MS threshold. This modified threshold model leads to the postulate that causes act at various time points to increase MS liability and induce MS pathology. The accumulation of MS pathology sometimes leads to a diagnosis of clinical MS. One implication of this model is that the MS pathology in clinical MS and in some with possible MS differs only in the extent but not in the type of CNS injury. Thus, it may be possible to obtain insight into the causative environmental factors that increase MS liability and induce MS pathology by focusing on patients who have clinical MS; some environmental factors that induce new lesions in patients with clinical MS may be identical to those that induce MS pathology in genetically susceptible individuals who do not have clinical MS. Identification of these causative factors has importance, as specific treatment may prevent the accumulation of MS pathology that leads to the significant CNS damage associated with clinical MS.

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood

PubMed Central

Reichborn-Kjennerud, T.; Czajkowski, N.; Ystrøm, E.; Ørstavik, R.; Aggen, S. H.; Tambs, K.; Torgersen, S.; Neale, M. C.; Røysamb, E.; Krueger, R. F.; Knudsen, G. P.; Kendler, K. S.

2015-01-01

Background Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. Method DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. Results The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. Conclusion ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD. PMID:26050739

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood.

PubMed

Reichborn-Kjennerud, T; Czajkowski, N; Ystrøm, E; Ørstavik, R; Aggen, S H; Tambs, K; Torgersen, S; Neale, M C; Røysamb, E; Krueger, R F; Knudsen, G P; Kendler, K S

2015-10-01

Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.

Dopamine and serotonin genetic risk scores predicting substance and nicotine use in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Groenman, Annabeth P.; Greven, Corina U.; van Donkelaar, Marjolein M.J.; Schellekens, Arnt; van Hulzen, Kimm J.E.; Rommelse, Nanda; Hartman, Catharina A.; Hoekstra, Pieter J.; Luman, Marjolein; Franke, Barbara; Faraone, Stephen V.; Oosterlaan, Jaap; Buitelaar, Jan K.

2015-01-01

Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways have been implicated in both ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that variations in dopamine and serotonin neurotransmission genes were involved in the genetic liability to develop SUDs/nicotine dependence in ADHD. The current study included participants with ADHD (n=280) who were originally part of the Dutch International Multicenter ADHD Genetics study. Participants were aged 5–15 years and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD, SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol use severity were based on semi-structured interviews and questionnaires. Genetic risk scores were created for both serotonergic and dopaminergic risk genes previously shown to be associated with ADHD and SUDs and/or nicotine dependence. The serotonin genetic risk score significantly predicted alcohol use severity. No significant serotonin*dopamine risk score or effect of stimulant medication was found. The current study adds to literature by providing insight into genetic underpinnings of the comorbidity of ADHD and SUDs. While the focus of the literature so far has been mostly on dopamine, our study suggests that serotonin may also play a role in the relationship between these disorders. PMID:25752199

The genetic epidemiology of personality disorders

PubMed Central

Reichborn-Kjennerud, Ted

2010-01-01

Genetic epidemiologic studies indicate that all ten personality disorders (PDs) classified on the DSM-IV axis II are modestly to moderately heritable. Shared environmental and nonadditive genetic factors are of minor or no importance. No sex differences have been identified. Multivariate studies suggest that the extensive comorbidity between the PDs can be explained by three common genetic and environmental risk factors. The genetic factors do not reflect the DSM-IV cluster structure, but rather: i) broad vulnerability to PD pathology or negative emotionality; ii) high impulsivity/low agreeableness; and iii) introversion. Common genetic and environmental liability factors contribute to comorbidity between pairs or clusters of axis I and axis II disorders. Molecular genetic studies of PDs, mostly candidate gene association studies, indicate that genes linked to neurotransmitter pathways, especially in the serotonergic and dopaminergic systems, are involved. Future studies, using newer methods like genome-wide association, might take advantage of the use of endophenotypes. PMID:20373672

Low extraversion and high neuroticism as indices of genetic and environmental risk for social phobia, agoraphobia, and animal phobia.

PubMed

Bienvenu, O Joseph; Hettema, John M; Neale, Michael C; Prescott, Carol A; Kendler, Kenneth S

2007-11-01

The authors examined the extent to which two major personality dimensions (extraversion and neuroticism) index the genetic and environmental risk for three phobias (social phobia, agoraphobia, and animal phobia) in twins ascertained from a large, population-based registry. Lifetime phobias and personality traits were assessed through diagnostic interview and self-report questionnaire, respectively, in 7,800 twins from female-female, male-male, and opposite-sex pairs. Sex-limited trivariate Cholesky structural equation models were used to decompose the correlations among extraversion, neuroticism, and each phobia. In the best-fitting models, genetic correlations were moderate and negative between extraversion and both social phobia and agoraphobia, and that between extraversion and animal phobia was effectively zero. Genetic correlations were high and positive between neuroticism and both social phobia and agoraphobia, and that between neuroticism and animal phobia was moderate. All of the genetic risk factors for social phobia and agoraphobia were shared with those that influence extraversion and neuroticism; in contrast, only a small proportion of the genetic risk factors for animal phobia (16%) was shared with those that influence personality. Shared environmental experiences were not a source of correlations between personality traits and phobias, and unique environmental correlations were relatively modest. Genetic factors that influence individual variation in extraversion and neuroticism appear to account entirely for the genetic liability to social phobia and agoraphobia, but not animal phobia. These findings underline the importance of both introversion (low extraversion) and neuroticism in some psychiatric disorders.

Abnormal Neural Activation to Faces in the Parents of Children with Autism

PubMed Central

Yucel, G. H.; Belger, A.; Bizzell, J.; Parlier, M.; Adolphs, R.; Piven, J.

2015-01-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the “Broad Autism Phenotype ” (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality (“BAP+”). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample

PubMed Central

Colvert, Emma; Tick, Beata; McEwen, Fiona; Stewart, Catherine; Curran, Sarah R.; Woodhouse, Emma; Gillan, Nicola; Hallett, Victoria; Lietz, Stephanie; Garnett, Tracy; Ronald, Angelica; Plomin, Robert; Rijsdijk, Frühling; Happé, Francesca; Bolton, Patrick

2016-01-01

IMPORTANCE Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population. OBJECTIVES To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD. DESIGN, SETTING, AND PARTICIPANTS We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview–Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs). MAIN OUTCOMES AND MEASURES Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis. RESULTS On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]). CONCLUSIONS AND RELEVANCE The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD. PMID:25738232

Genetic and environmental bases of the interplay between magical ideation and personality.

PubMed

Brambilla, Paolo; Fagnani, Corrado; Cecchetto, Filippo; Medda, Emanuela; Bellani, Marcella; Salemi, Miriam; Picardi, Angelo; Stazi, Maria Antonietta

2014-02-28

Sub-threshold psychotic symptoms are quite commonly present in general population. Among these, Magical Ideation (MI) has been proved to be a valid predictor of psychosis. However, the genetic and environmental influences on the interplay between MI and personality have not fully been explored. A total of 534 adult twins from the population-based Italian Twin Register were assessed for MI using the MI Scale (MIS) and for personality with the temperament and character inventory (TCI). A Multivariate Cholesky model was applied with Mx statistical program. The best-fitting model showed that additive genetic and unshared environmental factors explain approximately the same proportion of variance in MI, whereas a less strong genetic influence on personality traits emerged. Relevant correlations between MI and specific personality traits (novelty seeking, cooperativeness, self-directedness, self-transcendence) were found, suggesting shared influences for MI and these traits. Both genetic and environmental factors explained these correlations, with genetic factors playing a predominant role. Moderate-to-substantial genetic effects on MI and personality were found. Shared genetic and environmental effects underlie the phenotypic correlation between MI (psychosis-proneness) and personality traits, i.e. self-directedness (negative association) and self-transcendence (positive association), potentially representing predictive markers of psychosis liability related to schizotypy and personality. © 2013 Published by Elsevier Ireland Ltd.

Approaching confidentiality at a familial level in genomic medicine: a focus group study with healthcare professionals

PubMed Central

Dheensa, Sandi; Fenwick, Angela; Lucassen, Anneke

2017-01-01

Objectives Clinical genetics guidelines from 2011 conceptualise genetic information as confidential to families, not individuals. The normative consequence of this is that the family's interest is the primary consideration and genetic information is shared unless there are good reasons not to do so. We investigated healthcare professionals' (HCPs') views about, and reasoning around, individual and familial approaches to confidentiality and how such views influenced their practice. Method 16 focus groups with 80 HCPs working in/with clinical genetics services were analysed, drawing on grounded theory. Results Participants raised seven problems with, and arguments against, going beyond the individual approach to confidentiality. These problems fell into two overlapping categories: ‘relationships’ and ‘structures’. Most participants had never considered ways to—or thought it was impossible to—treat familial genetic information and personal information differently. They worried that putting the familial approach into practice could disrupt family dynamics and erode patient trust in the health service. They also thought they had insufficient resources to share information and feared that sharing might change the standard of care and make them more vulnerable to liability. Conclusions A familial approach to confidentiality has not been accepted or adopted as a standard, but wider research suggests that some of the problems HCPs perceived are surmountable and sharing in the interest of the family can be achieved. However, further research is needed to explore how personal and familial genetic information can be separated in practice. Our findings are relevant to HCPs across health services who are starting to use genome tests as part of their routine investigations. PMID:28159847

Associations Between Fetal Growth and Self-Perceived Health Throughout Adulthood: A Co-twin Control Study.

PubMed

Mosing, Miriam A; Cnattingius, Sven; Gatz, Margaret; Neiderhiser, Jenae M; Pedersen, Nancy L

2016-05-01

The literature shows evidence for long-lasting effects of low birth weight (LBW) on many health outcomes, but little is known about effects on self-perceived health. Findings are mixed and studies are small, mostly focusing on LBW effects on health outcomes before adulthood. Further, as LBW and most health conditions including self-perceived health are partly heritable, associations between birth weight (BW) and adverse health outcomes may also be due to shared genetic as well as other (pre- and postnatal) unmeasured environmental influences. We explored LBW effects on self-perceived health in early and later adulthood using a very large and genetically informative sample of more than 50,000 Swedish twins. In addition, analyses within twin pairs (the co-twin control design) were used to examine potential associations between BW and the offspring's risk for poor self-perceived health independent of shared environmental or genetic factors, evidence which is critical for the understanding of underlying mechanisms. Results showed that lower BW was significantly associated with poorer self-perceived health during adulthood, although the effect size was small. Co-twin control analyses suggested that this increased risk may be due to shared underlying liability (environmental or genetic) rather than a direct effect of BW, but findings were not conclusive.

Electric and Hybrid Electric Vehicle Technologies

DTIC Science & Technology

1998-06-30

participants; car sharing logistics; liability issues; billing and col- lecting user fees; service and maintenance support; data acquisition; and...driven on the freeway, and their circumstances had changed. Among the challenges facing station-car and car - sharing programs that use EVs rather than...funding; selection and training of users; many different types of participants; car sharing logistics; liability issues; billing and collecting user

24 CFR 203.422 - Right and liability under Mutual Mortgage Insurance Fund.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Mortgage Insurance Fund and Distributive Shares § 203.422 Right and liability under Mutual Mortgage... to any liability arising under the mutuality of the Mutual Mortgage Insurance Fund. ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Right and liability under Mutual...

24 CFR 203.422 - Right and liability under Mutual Mortgage Insurance Fund.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Mortgage Insurance Fund and Distributive Shares § 203.422 Right and liability under Mutual Mortgage... to any liability arising under the mutuality of the Mutual Mortgage Insurance Fund. ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Right and liability under Mutual...

Genetic Liability to Disability Pension in Women and Men: A Prospective Population-Based Twin Study

PubMed Central

Narusyte, Jurgita; Ropponen, Annina; Silventoinen, Karri; Alexanderson, Kristina; Kaprio, Jaakko; Samuelsson, Åsa; Svedberg, Pia

2011-01-01

Background Previous studies of risk factors for disability pension (DP) have mainly focused on psychosocial, or environmental, factors, while the relative importance of genetic effects has been less studied. Sex differences in biological mechanisms have not been investigated at all. Methods The study sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs, born 1928–1958, who were followed during 1993–2008. Data on DP, including diagnoses, were obtained from the National Social Insurance Agency. Within-pair similarity in liability to DP was assessed by calculating intraclass correlations. Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty modeling. Results During follow-up, 7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed pairs were more similar than opposite-sexed pairs. The best-fitting model indicated that genetic factors contributed 49% (95% CI: 39–59) to the variance in DP due to mental diagnoses, 35% (95% CI: 29–41) due to musculoskeletal diagnoses, and 27% (95% CI: 20–33) due to all other diagnoses. In both sexes, genetic effects common to all ages explained one-third, whereas age-specific factors almost two-thirds, of the total variance in liability to DP irrespective of diagnosis. Sex differences in liability to DP were indicated, in that partly different sets of genes were found to operate in women and men, even though the magnitude of genetic variance explained was equal for both sexes. Conclusions The findings of the study suggest that genetic effects are important for liability to DP due to different diagnoses. Moreover, genetic contributions to liability to DP tend to differ between women and men, even though the overall relative contribution of genetic influences does not differ by sex. Hence, the pathways leading to DP might differ between women and men. PMID:21850258

Developmental Markers of Genetic Liability to Autism in Parents: A Longitudinal, Multigenerational Study.

PubMed

Losh, Molly; Martin, Gary E; Lee, Michelle; Klusek, Jessica; Sideris, John; Barron, Sheila; Wassink, Thomas

2017-03-01

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of 139 parents of individuals with ASD were studied, along with their children with ASD and 28 controls. Parents' childhood records in the domains of language, reading, and math were studied from grades K-12. Results indicated that relatively lower performance and slower development of skills (particularly language related skills), and an uneven rate of development across domains predicted ASD endophenotypes in adulthood for parents, and the severity of clinical symptoms in children with ASD. These findings may mark childhood indicators of genetic liability to ASD in parents, that could inform understanding of the subclinical expression of ASD genetic liability.

Abnormal Neural Activation to Faces in the Parents of Children with Autism.

PubMed

Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

2015-12-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Genetic and Environmental Influences on Smoking Behavior across Adolescence and Young Adulthood in the Virginia Twin Study of Adolescent Behavioral Development and the Transitions to Substance Abuse Follow-Up

PubMed Central

Do, Elizabeth K.; Prom-Wormley, Elizabeth C.; Eaves, Lindon J.; Silberg, Judy L.; Miles, Donna R.; Maes, Hermine H.

2016-01-01

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role. PMID:25662421

Genetic and Environmental Influences on Smoking Behavior across Adolescence and Young Adulthood in the Virginia Twin Study of Adolescent Behavioral Development and the Transitions to Substance Abuse Follow-Up.

PubMed

Do, Elizabeth K; Prom-Wormley, Elizabeth C; Eaves, Lindon J; Silberg, Judy L; Miles, Donna R; Maes, Hermine H

2015-02-01

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role.

Genetic contribution to patent ductus arteriosus in the premature newborn.

PubMed

Bhandari, Vineet; Zhou, Gongfu; Bizzarro, Matthew J; Buhimschi, Catalin; Hussain, Naveed; Gruen, Jeffrey R; Zhang, Heping

2009-02-01

The most common congenital heart disease in the newborn population, patent ductus arteriosus, accounts for significant morbidity in preterm newborns. In addition to prematurity and environmental factors, we hypothesized that genetic factors play a significant role in this condition. The objective of this study was to quantify the contribution of genetic factors to the variance in liability for patent ductus arteriosus in premature newborns. A retrospective study (1991-2006) from 2 centers was performed by using zygosity data from premature twins born at < or =36 weeks' gestational age and surviving beyond 36 weeks' postmenstrual age. Patent ductus arteriosus was diagnosed by echocardiography at each center. Mixed-effects logistic regression was used to assess the effect of specific covariates. Latent variable probit modeling was then performed to estimate the heritability of patent ductus arteriosus, and mixed-effects probit modeling was used to quantify the genetic component. We obtained data from 333 dizygotic twin pairs and 99 monozygotic twin pairs from 2 centers (Yale University and University of Connecticut). Data on chorioamnionitis, antenatal steroids, gestational age, body weight, gender, respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, oxygen supplementation, and bronchopulmonary dysplasia were comparable between monozygotic and dizygotic twins. We found that gestational age, respiratory distress syndrome, and institution were significant covariates for patent ductus arteriosus. After controlling for specific covariates, genetic factors or the shared environment accounted for 76.1% of the variance in liability for patent ductus arteriosus. Preterm patent ductus arteriosus is highly familial (contributed to by genetic and environmental factors), with the effect being mainly environmental, after controlling for known confounders.

Developmental Markers of Genetic Liability to Autism in Parents: A Longitudinal, Multigenerational Study

ERIC Educational Resources Information Center

Losh, Molly; Martin, Gary E.; Lee, Michelle; Klusek, Jessica; Sideris, John; Barron, Sheila; Wassink, Thomas

2017-01-01

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of…

31 CFR 321.15 - Liability for losses.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Liability for losses. 321.15 Section... INSTITUTIONS OF UNITED STATES SAVINGS BONDS AND UNITED STATES SAVINGS NOTES (FREEDOM SHARES) Losses Resulting From Erroneous Payments § 321.15 Liability for losses. Under the governing statute, as amended (31 U.S...

The heritability of cluster A personality disorders assessed by both personal interview and questionnaire.

PubMed

Kendler, Kenneth S; Myers, John; Torgersen, Svenn; Neale, Michael C; Reichborn-Kjennerud, Ted

2007-05-01

Personality disorders (PDs) as assessed by questionnaires and personal interviews are heritable. However, we know neither how much unreliability of measurement impacts on heritability estimates nor whether the genetic and environmental risk factors assessed by these two methods are the same. We wish to know whether the same set of PD vulnerability factors are assessed by these two methods. A total of 3334 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel (NIPHTP) completed a questionnaire containing 91 PD items. One to 6 years later, 1386 of these pairs were interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV). Self-report items predicting interview results were selected by regression. Measurement models were fitted using Mx. In the best-fit models, the latent liabilities to paranoid personality disorder (PPD), schizoid personality disorder (SPD) and schizotypal personality disorder (STPD) were all highly heritable with no evidence of shared environmental effects. For PPD and STPD, only unique environmental effects were specific to the interview measure whereas both environmental and genetic effects were found to be specific to the questionnaire assessment. For SPD, the best-fit model contained genetic and environmental effects specific to both forms of assessment. The latent liabilities to the cluster A PDs are highly heritable but are assessed by current methods with only moderate reliability. The personal interviews assessed the genetic risk for the latent trait with excellent specificity for PPD and STPD and good specificity for SPD. However, for all three PDs, the questionnaires were less specific, also indexing an independent set of genetic risk factors.

Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems.

PubMed

Yeung, Ellen W; Craggs, Jason G; Gizer, Ian R

2017-11-01

Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence has suggested that neuroadaptive processes characterized by reward deficit and stress surfeit are involved in the development of AUD and pain chronification. Neurological data suggest that shared genetic architecture associated with the reward and stress systems may contribute to the comorbidity of AUD and CP. This monograph first delineates the prevailing theories of the development of AUD and pain chronification focusing on the reward and stress systems. It then provides a brief summary of relevant neurological findings followed by an evaluation of evidence documented by molecular genetic studies. Candidate gene association studies have provided some initial support for the genetic overlap between AUD and CP; however, these results must be interpreted with caution until studies with sufficient statistical power are conducted and replications obtained. Genomewide association studies have suggested a number of genes (e.g., TBX19, HTR7, and ADRA1A) that are either directly or indirectly related to the reward and stress systems in the AUD and CP literature. Evidence reviewed in this monograph suggests that shared genetic liability underlying the comorbidity between AUD and CP, if present, is likely to be complex. As the advancement in molecular genetic methods continues, future studies may show broader central nervous system involvement in AUD-CP comorbidity. Copyright © 2017 by the Research Society on Alcoholism.

Current Parental Depression and Offspring Perceived Self-Competence: A Quasi-Experimental Examination

PubMed Central

Class, Quetzal A.; D’Onofrio, Brian M.; Singh, Amber L.; Ganiban, Jody M.; Spotts, E. L.; Lichtenstein, Paul; Reiss, David; Neiderhiser, Jenae M.

2013-01-01

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52%) and female offspring aged 15.7 ± 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins (CoT) designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended-family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression. PMID:22692226

Current parental depression and offspring perceived self-competence: a quasi-experimental examination.

PubMed

Class, Quetzal A; D'Onofrio, Brian M; Singh, Amber L; Ganiban, Jody M; Spotts, E L; Lichtenstein, Paul; Reiss, David; Neiderhiser, Jenae M

2012-09-01

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52 %) and female offspring aged 15.7 ± 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression.

Genetic and environmental influences on the transmission of parental depression to children's depression and conduct disturbance: an extended Children of Twins study.

PubMed

Silberg, Judy L; Maes, Hermine; Eaves, Lindon J

2010-06-01

Despite the increased risk of depression and conduct problems in children of depressed parents, the mechanism by which parental depression affects their children's behavioral and emotional functioning is not well understood. The present study was undertaken to determine whether parental depression represents a genuine environmental risk factor in children's psychopathology, or whether children's depression/conduct can be explained as a secondary consequence of the genetic liability transmitted from parents to their offspring. Children of Twins (COT) data collected on 2,674 adult female and male twins, their spouses, and 2,940 of their children were used to address whether genetic and/or family environmental factors best account for the association between depression in parents and depression and conduct problems in their children. Data collected on juvenile twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) were also included to estimate child-specific genetic and environmental influences apart from those effects arising from the transmission of the parental depression itself. The fit of alternative Children of Twin models were evaluated using the statistical program Mx. The most compelling model for the association between parental and juvenile depression was a model of direct environmental risk. Both family environmental and genetic factors accounted for the association between parental depression and child conduct disturbance. These findings illustrate how a genetically mediated behavior such as parental depression can have both an environmental and genetic impact on children's behavior. We find developmentally specific genetic factors underlying risk to juvenile and adult depression. A shared genetic liability influences both parental depression and juvenile conduct disturbance, implicating child conduct disturbance (CD) as an early indicator of genetic risk for depression in adulthood. In summary, our analyses demonstrate differences in the impact of parental depression on different forms of child psychopathology, and at various stages of development.

Genetic and environmental influences on the transmission of parental depression to children’s depression and conduct disturbance: An extended Children of Twins study

PubMed Central

Silberg, Judy L.; Maes, Hermine; Eaves, Lindon J.

2010-01-01

Background Despite the increased risk of depression and conduct problems in children of depressed parents, the mechanism by which parental depression affects their children’s behavioral and emotional functioning is not well understood. The present study was undertaken to determine whether parental depression represents a genuine environmental risk factor in children’s psychopathology, or whether children’s depression/conduct can be explained as a secondary consequence of the genetic liability transmitted from parents to their offspring. Methods Children of Twins (COT) data collected on 2,674 adult female and male twins, their spouses, and 2,940 of their children were used to address whether genetic and/or family environmental factors best account for the association between depression in parents and depression and conduct problems in their children. Data collected on juvenile twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) were also included to estimate child-specific genetic and environmental influences apart from those effects arising from the transmission of the parental depression itself. The fit of alternative Children of Twin models were evaluated using the statistical program Mx. Results The most compelling model for the association between parental and juvenile depression was a model of direct environmental risk. Both family environmental and genetic factors accounted for the association between parental depression and child conduct disturbance. Conclusions These findings illustrate how a genetically mediated behavior such as parental depression can have both an environmental and genetic impact on children’s behavior. We find developmentally specific genetic factors underlying risk to juvenile and adult depression. A shared genetic liability influence both parental depression and juvenile conduct disturbance, implicating child CD as an early indicator of genetic risk for depression in adulthood. In summary, our analyses demonstrate differences in the impact of parental depression on different forms of child psychopathology, and at various stages of development. PMID:20163497

Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive-Compulsive, and Hoarding Symptoms.

PubMed

Zilhão, Nuno R; Smit, Dirk J; Boomsma, Dorret I; Cath, Danielle C

2016-01-01

Hoarding, obsessive-compulsive disorder (OCD), and Tourette's disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific environmental factors unshared with OCS and HD.

A twin study of body dysmorphic concerns.

PubMed

Monzani, B; Rijsdijk, F; Anson, M; Iervolino, A C; Cherkas, L; Spector, T; Mataix-Cols, D

2012-09-01

Dysmorphic concern refers to an excessive preoccupation with a perceived or slight defect in physical appearance. It lies on a continuum of severity from no or minimal concerns to severe concerns over one's appearance. The present study examined the heritability of dysmorphic concerns in a large sample of twins. Twins from the St Thomas UK twin registry completed a valid and reliable self-report measure of dysmorphic concerns, which also includes questions about perceived body odour and malfunction. Twin modelling methods (female twins only, n=3544) were employed to decompose the variance in the liability to dysmorphic concerns into additive genetic, shared and non-shared environmental factors. Model-fitting analyses showed that genetic factors accounted for approximately 44% [95% confidence intervals (CI) 36-50%] of the variance in dysmorphic concerns, with non-shared environmental factors and measurement error accounting for the remaining variance (56%; 95% CI 50-63%). Shared environmental factors were negligible. The results remained unchanged when excluding individuals reporting an objective medical condition/injury accounting for their concern in physical appearance. Over-concern with a perceived or slight defect in physical appearance is a heritable trait, with non-shared environmental factors also playing an important role in its causation. The results are relevant for various psychiatric disorders characterized by excessive concerns in body appearance, odour or function, including but not limited to body dysmorphic disorder.

Reasonable Foreseeability and Liability in Relation to Genetically Modified Organisms

ERIC Educational Resources Information Center

Khoury, Lara; Smyth, Stuart

2007-01-01

This article examines problems that may arise when addressing liability resulting from the genetic modification of microbes, animals, and plants. More specifically, it evaluates how uncertainties relating to the outcomes of these biotechnological innovations affect--or may affect--the courts' application of the reasonable foreseeability…

Privacy and Biobanking in China: A Case of Policy in Transition.

PubMed

Chen, Haidan; Chan, Benny; Joly, Yann

2015-01-01

Disease-based biobanks have operated in hospitals and research institutes in China for decades, and China has recently embarked on a plan to establish further biobank networks with the aim of promoting data sharing among the existing biobanks. Although the Chinese Constitution has only recently begun to recognize individual privacy as a distinct and independent constitutional right, biobanking in China has been loosely regulated under a patchwork of sometimes overlapping laws (such as the Interim Measures for the Administration of Human Genetic Resources) and regulatory instruments, as well as and the policies of individual biobanks and networks of biobanks (such as the Shanghai Biobank Network Guidelines). A Draft Ordinance on Human Genetics Resources is currently being developed that will deal in more detail than previous laws with issues such as management measures, legal liability, and punishment for violations. International data sharing will be tightly regulated under this new law, and individual biobanks' policies such as the Shanghai Guidelines may choose to regulate such sharing even more. In contrast with national regulatory instruments, the Shanghai Guidelines also contain detailed de-identification policies, and explicitly endorse broad consent. © 2015 American Society of Law, Medicine & Ethics, Inc.

A multivariate twin study of trait mindfulness, depressive symptoms, and anxiety sensitivity.

PubMed

Waszczuk, Monika A; Zavos, Helena M S; Antonova, Elena; Haworth, Claire M; Plomin, Robert; Eley, Thalia C

2015-04-01

Mindfulness-based therapies have been shown to be effective in treating depression and reducing cognitive biases. Anxiety sensitivity is one cognitive bias that may play a role in the association between mindfulness and depressive symptoms. It refers to an enhanced sensitivity toward symptoms of anxiety, with a belief that these are harmful. Currently, little is known about the mechanisms underpinning the association between mindfulness, depression, and anxiety sensitivity. The aim of this study was to examine the role of genetic and environmental factors in trait mindfulness, and its genetic and environmental overlap with depressive symptoms and anxiety sensitivity. Over 2,100 16-year-old twins from a population-based study rated their mindfulness, depressive symptoms, and anxiety sensitivity. Twin modeling analyses revealed that mindfulness is 32% heritable and 66% due to nonshared environmental factors, with no significant influence of shared environment. Genetic influences explained over half of the moderate phenotypic associations between low mindfulness, depressive symptoms, and anxiety sensitivity. About two-thirds of genetic influences and almost all nonshared environmental influences on mindfulness were independent of depression and anxiety sensitivity. This is the first study to show that both genes and environment play an important role in the etiology of mindfulness in adolescence. Future research should identify the specific environmental factors that influence trait mindfulness during development to inform targeted treatment and resilience interventions. Shared genetic liability underpinning the co-occurrence of low mindfulness, depression, and anxiety sensitivity suggests that the biological pathways shared between these traits should also be examined. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

Combat Exposure Severity as a Moderator of Genetic and Environmental Liability to Posttraumatic Stress Disorder

PubMed Central

Wolf, Erika J.; Mitchell, Karen S.; Koenen, Karestan C.; Miller, Mark W.

2014-01-01

Background Twin studies of veterans and adults suggest that approximately 30–46% of the variance in posttraumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to examine if the effect of genetic and environmental factors that contribute to the etiology PTSD were dependent on level of combat exposure. Methods The sample was drawn from the Vietnam Era Twin Registry and included 620 male-male twin pairs who served in the U.S. Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure. Results Biometric modeling revealed that the effect of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure. Conclusions Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and other environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations. PMID:24001428

Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder.

PubMed

Wolf, E J; Mitchell, K S; Koenen, K C; Miller, M W

2014-05-01

Twin studies of veterans and adults suggest that approximately 30-46% of the variance in post-traumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to determine whether the effects of genetic and environmental factors that contribute to the etiology of PTSD are dependent on the level of combat exposure. The sample was drawn from the Vietnam Era Twin Registry (VETR) and included 620 male-male twin pairs who served in the US Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure. Biometric modeling revealed that the effects of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure. Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations.

Shared Genetics of Temporomandibular Disorder Pain and Neck Pain: Results of a Twin Study.

PubMed

Visscher, Corine M; Schouten, Maarten J; Ligthart, Lannie; van Houtem, Caroline Mhh; de Jongh, Ad; Boomsma, Dorret I

2018-03-06

(1) To examine the heritability of TMD pain and of neck pain; and (2) to estimate the potential overlap in genetic and environmental factors influencing TMD pain and neck pain. Data from 2,238 adult female twins who completed a survey on TMD pain and neck pain were analyzed. The total variance of TMD pain and neck pain was decomposed into variance attributable to additive genetic effects and nonshared environmental effects. Bivariate structural equation modeling was applied to estimate trait-specific and genetic effects shared between traits. The prevalence of TMD pain and neck pain was 8.6% and 46.8%, respectively, while 6.7% of the twins reported both TMD pain and neck pain. The phenotypic correlation between TMD pain and neck pain, based on a liability threshold model, was 0.43 (95% confidence interval [CI] 0.34 to 0.51). The heritability for TMD was 0.35 (0.17 to 0.51), and for neck pain was 0.33 (0.23 to 0.43). The genetic correlation between TMD pain and neck pain was 0.64 (0.35 to 1.00), and the environmental correlation was 0.32 (0.14 to 0.48). This study shows that variation in TMD pain and neck pain can in part be attributed to genes. The comorbidity between them is partly explained by genes that influence both traits and partly by the same environmental factors.

Age at First Use and Later Substance Use Disorder: Shared Genetic and Environmental Pathways for Nicotine, Alcohol, and Cannabis

PubMed Central

Richmond-Rakerd, Leah S.; Slutske, Wendy S.; Lynskey, Michael T.; Agrawal, Arpana; Madden, Pamela A.F.; Bucholz, Kathleen K.; Heath, Andrew C.; Statham, Dixie J.; Martin, Nicholas G.

2016-01-01

Behavioral genetic studies have provided insights into why early substance use initiation is associated with increased risk for disorder. Few genetically-informative studies, however, have operationalized initiation as the timing of first use and simultaneously modeled the timing of initiation and problematic use of multiple substances. Such research can help capture the risk associated with early initiation and determine the extent to which genetic and environmental risk generalizes across substances. This study utilized a behavior genetic approach to examine the relation between the age of substance use initiation and symptoms of substance use disorder. Participants were 7,285 monozygotic and dizygotic twins (40% male, mean age at interview=30.6) from the Australian Twin Registry who reported on their ages of tobacco, alcohol, and cannabis initiation and symptoms of DSM-IV nicotine dependence, alcohol use disorder, and cannabis use disorder. Biometric modeling was conducted to (a) determine the structure of genetic and environmental influences on initiation and disorder and (b) examine their genetic and environmental overlap. The latent structure of initiation differed across men and women. The familial covariance between initiation and disorder was genetic among men and genetic and environmental among women, suggesting that the relation between first substance use and disorder is partly explained by a shared liability. After accounting for familial overlap, significant unique environmental correlations were observed, indicating that the age of initiation of multiple drugs may directly increase risk for substance-related problems. Results support the utility of conceptualizing initiation in terms of age and of adopting a multivariate approach. PMID:27537477

A longitudinal, population-based twin study of avoidant and obsessive-compulsive personality disorder traits from early to middle adulthood

PubMed Central

Gjerde, L. C.; Czajkowski, N.; Røysamb, E.; Ystrom, E.; Tambs, K.; Aggen, S. H.; Ørstavik, R. E.; Kendler, K. S.; Reichborn-Kjennerud, T.; Knudsen, G. P.

2015-01-01

Background The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability. Method AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits. Results For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2. Conclusion Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes. PMID:26273730

A longitudinal, population-based twin study of avoidant and obsessive-compulsive personality disorder traits from early to middle adulthood.

PubMed

Gjerde, L C; Czajkowski, N; Røysamb, E; Ystrom, E; Tambs, K; Aggen, S H; Ørstavik, R E; Kendler, K S; Reichborn-Kjennerud, T; Knudsen, G P

2015-12-01

The phenotypic stability of avoidant personality disorder (AVPD) and obsessive-compulsive personality disorder (OCPD) has previously been found to be moderate. However, little is known about the longitudinal structure of genetic and environmental factors for these disorders separately and jointly, and to what extent genetic and environmental factors contribute to their stability. AVPD and OCPD criteria were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins (1385 pairs, 23 singletons) from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 (986 pairs, 310 singletons) of these on average 10 years later at wave 2. Longitudinal biometric models were fitted to AVPD and OCPD traits. For twins who participated at both time-points, the number of endorsed sub-threshold criteria for both personality disorders (PDs) decreased 31% from wave 1 to wave 2. Phenotypic correlations between waves were 0.54 and 0.37 for AVPD and OCPD, respectively. The heritability estimates of the stable PD liabilities were 0.67 for AVPD and 0.53 for OCPD. The genetic correlations were 1.00 for AVPD and 0.72 for OCPD, while the unique environmental influences correlated 0.26 and 0.23, respectively. The correlation between the stable AVPD and OCPD liabilities was 0.39 of which 63% was attributable to genetic influences. Shared environmental factors did not significantly contribute to PD variance at either waves 1 or 2. Phenotypic stability was moderate for AVPD and OCPD traits, and genetic factors contributed more than unique environmental factors to the stability both within and across phenotypes.

Direct-to-consumer genetic testing for addiction susceptibility: a premature commercialisation of doubtful validity and value.

PubMed

Mathews, Rebecca; Hall, Wayne; Carter, Adrian

2012-12-01

Genetic research on addiction liability and pharmacogenetic research on treatments for addiction have identified some genetic variants associated with disease risk and treatment. Genetic testing for addiction liability and treatment response has not been used widely in clinical practice because most of the genes identified only modestly predict addiction risk or treatment response. However, many of these genetic tests have been commercialized prematurely and are available direct to the consumer (DTC). The easy availability of DTC tests for addiction liability and lack of regulation over their use raises a number of ethical concerns. Of paramount concern is the limited predictive power and clinical utility of these tests. Many DTC testing companies do not provide the consumer with the necessary genetic counselling to assist them in interpreting and acting on their test results. They may also engage in misleading marketing to entice consumers to purchase their products. Consumers' genetic information may be vulnerable to misuse by third parties, as there are limited standards to protect the privacy of the genetic information. Non-consensual testing and inappropriate testing of minors may also occur. The United States Food and Drug Administration plans to regulate DTC genetic tests. Based on the ethical concerns we discuss below, we believe there is a strong case for regulation of DTC genetic tests for addiction liability and treatment response. We argue that until this occurs, these tests have more potential to cause harm than to contribute to improved prevention and treatment of addiction. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Medicaid Eligibility

MedlinePlus

... recover for other Medicaid benefits, except for Medicare cost-sharing benefits paid on behalf of Medicare Savings Program beneficiaries. Third Party Liability: Third Party Liability (TPL) refers to third ... or all of the cost of medical services provided to a Medicaid beneficiary. ...

Social Relationships Moderate Genetic Influences on Heavy Drinking in Young Adulthood.

PubMed

Barr, Peter B; Salvatore, Jessica E; Maes, Hermine H; Korhonen, Tellervo; Latvala, Antti; Aliev, Fazil; Viken, Richard; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

2017-11-01

Social relationships, such as committed partnerships, limit risky behaviors like heavy drinking, in part, because of increased social control. The current analyses examine whether involvement in committed relationships or social support extend beyond a main effect to limit genetic liability in heavy drinking (gene-environment interaction) during young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (n = 3,269), we tested whether involvement in romantic partnerships or social support moderated genetic influences on heavy drinking using biometric twin modeling for gene-environment interaction. Involvement in a romantic partnership was associated with a decline in genetic variance in both males and females, although the overall magnitude of genetic influence was greater in males. Sex differences emerged for social support: increased social support was associated with increased genetic influence for females and reduced genetic influence for males. These findings demonstrate that social relationships are important moderators of genetic influences on young adult alcohol use. Mechanisms of social control that are important in limiting genetic liability during adolescence extend into young adulthood. In addition, although some relationships limit genetic liability equally, others, such as extensive social networks, may operate differently across sex.

A Swedish national twin study of criminal behavior and its violent, white-collar and property subtypes.

PubMed

Kendler, K S; Maes, H H; Lönn, S L; Morris, N A; Lichtenstein, P; Sundquist, J; Sundquist, K

2015-08-01

We sought to clarify the etiological contribution of genetic and environmental factors to total criminal behavior (CB) measured as criminal convictions in men and women, and to violent (VCB), white-collar (WCCB) and property criminal behavior (PCB) in men only. In 21 603 twin pairs from the Swedish Twin Registry, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. Twin modeling was performed using the OpenMx package. For all criminal convictions, heritability was estimated at around 45% in both sexes, with the shared environment accounting for 18% of the variance in liability in females and 27% in males. The correlation of these risk factors across sexes was estimated at +0.63. In men, the magnitudes of genetic and environmental influence were similar in the three criminal conviction subtypes. However, for violent and white-collar convictions, nearly half and one-third of the genetic effects were respectively unique to that criminal subtype. About half of the familial environmental effects were unique to property convictions. The familial aggregation of officially recorded CB is substantial and results from both genetic and familial environmental factors. These factors are moderately correlated across the sexes suggesting that some genetic and environmental influences on criminal convictions are unique to men and to women. Violent criminal behavior and property crime are substantially influenced respectively by genetic and shared environmental risk factors unique to that criminal subtype.

The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity.

PubMed

Distel, Marijn A; Trull, Timothy J; Willemsen, Gonneke; Vink, Jacqueline M; Derom, Catherine A; Lynskey, Michael; Martin, Nicholas G; Boomsma, Dorret I

2009-12-15

Recently, the nature of personality disorders and their relationship with normal personality traits has received extensive attention. The five-factor model (FFM) of personality, consisting of the personality traits neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness, is one of the proposed models to conceptualize personality disorders as maladaptive variants of continuously distributed personality traits. The present study examined the phenotypic and genetic association between borderline personality and FFM personality traits. Data were available for 4403 monozygotic twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and Australian families. Broad-sense heritability estimates for neuroticism, agreeableness, conscientiousness, extraversion, openness to experience, and borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively. Phenotypic correlations between borderline personality and the FFM personality traits ranged from .06 for openness to experience to .68 for neuroticism. Multiple regression analyses showed that a combination of high neuroticism and low agreeableness best predicted borderline personality. Multivariate genetic analyses showed the genetic factors that influence individual differences in neuroticism, agreeableness, conscientiousness, and extraversion account for all genetic liability to borderline personality. Unique environmental effects on borderline personality, however, were not completely shared with those for the FFM traits (33% is unique to borderline personality). Borderline personality shares all genetic variation with neuroticism, agreeableness, conscientiousness, and extraversion. The unique environmental influences specific to borderline personality may cause individuals with a specific pattern of personality traits to cross a threshold and develop borderline personality.

Grounding the Management of Liabilities in the Risk Analysis Framework

ERIC Educational Resources Information Center

Phillips, Peter W. B.; Smyth, Stuart

2007-01-01

Discussions of socioeconomic liability and compensation must necessarily start from an understanding of the socioeconomic, legal, and scientific basis for identifying, assessing, managing, and apportioning blame for hazards related to innovations. Public discussions about the nature of the liability challenge related to genetically modified (GM)…

Genetic Liability, Environment, and the Development of Fussiness in Toddlers: The Roles of Maternal Depression and Parental Responsiveness

ERIC Educational Resources Information Center

Natsuaki, Misaki N.; Ge, Xiaojia; Leve, Leslie D.; Neiderhiser, Jenae M.; Shaw, Daniel S.; Conger, Rand D.; Scaramella, Laura V.; Reid, John B.; Reiss, David

2010-01-01

Using a longitudinal, prospective adoption design, the authors of this study examined the effects of the environment (adoptive parents' depressive symptoms and responsiveness) and genetic liability of maternal depression (inferred by birth mothers' major depressive disorder [MDD]) on the development of fussiness in adopted children between 9 and…

Common and specific liability to addiction: approaches to association studies of opioid addiction.

PubMed

Nielsen, David A; Kreek, Mary Jeanne

2012-06-01

Opioid addiction, whether to opiates such as heroin and morphine, and/or to non-medical use of opioids, is a major problem worldwide. Although drug-induced and environmental factors are essential for the liability to develop opioid addiction, the genetic background of an individual is now known also to play a substantial role. The overall goal of this article is to address the common and specific liabilities to addiction in the context of approaches to studies of one addiction, opioid addiction. Literature on identifying genetic variants that may play a role in the development of opioid addiction was reviewed. A substantial number of genetic variants have been reported to be associated with opioid addiction. No single variant has been found in any of the reported GWAS studies with a substantial effect size on the liability to develop heroin addiction. It appears that there is a complex interaction of a large number of variants, some rare, some common, which interact with the environment and in response to specific drugs of abuse to increase the liability of developing opioid addiction. In spite of the inherent difficulties in obtaining large well-phenotyped cohorts for genetic studies, new findings have been reported that are being used to develop testable hypotheses into the biological basis of opioid addiction. Copyright © 2012. Published by Elsevier Ireland Ltd.

Quantitative genetic analysis of injury liability in infants and toddlers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, K.; Matheny, A.P. Jr.

1995-02-27

A threshold model of latent liability was applied to infant and toddler twin data on total count of injuries sustained during the interval from birth to 36 months of age. A quantitative genetic analysis of estimated twin correlations in injury liability indicated strong genetic dominance effects, but no additive genetic variance was detected. Because interpretations involving overdominance have little research support, the results may be due to low order epistasis or other interaction effects. Boys had more injuries than girls, but this effect was found only for groups whose parents were prompted and questioned in detail about their children`s injuries.more » Activity and impulsivity are two behavioral predictors of childhood injury, and the results are discussed in relation to animal research on infant and adult activity levels, and impulsivity in adult humans. Genetic epidemiological approaches to childhood injury should aid in targeting higher risk children for preventive intervention. 30 refs., 4 figs., 3 tabs.« less

Age at first use and later substance use disorder: Shared genetic and environmental pathways for nicotine, alcohol, and cannabis.

PubMed

Richmond-Rakerd, Leah S; Slutske, Wendy S; Lynskey, Michael T; Agrawal, Arpana; Madden, Pamela A F; Bucholz, Kathleen K; Heath, Andrew C; Statham, Dixie J; Martin, Nicholas G

2016-10-01

Behavioral genetic studies have provided insights into why early substance use initiation is associated with increased risk for disorder. Few genetically informative studies, however, have operationalized initiation as the timing of first use and simultaneously modeled the timing of initiation and problematic use of multiple substances. Such research can help capture the risk associated with early initiation and determine the extent to which genetic and environmental risk generalizes across substances. This study utilized a behavior genetic approach to examine the relation between the age of substance use initiation and symptoms of substance use disorder. Participants were 7,285 monozygotic and dizygotic twins (40% male, mean age at interview = 30.6 years) from the Australian Twin Registry who reported on their ages of tobacco, alcohol, and cannabis initiation and symptoms of Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV) nicotine dependence, alcohol use disorder, and cannabis use disorder. Biometric modeling was conducted to (a) determine the structure of genetic and environmental influences on initiation and disorder and (b) examine their genetic and environmental overlap. The latent structure of initiation differed across men and women. The familial covariance between initiation and disorder was genetic among men and genetic and environmental among women, suggesting that the relation between first substance use and disorder is partly explained by a shared liability. After accounting for familial overlap, significant unique environmental correlations were observed, indicating that the age of initiation of multiple drugs may directly increase risk for substance-related problems. Results support the utility of conceptualizing initiation in terms of age and of adopting a multivariate approach. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: a twin study of specific psychotic experiences in adolescence.

PubMed

Zavos, Helena M S; Freeman, Daniel; Haworth, Claire M A; McGuire, Philip; Plomin, Robert; Cardno, Alastair G; Ronald, Angelica

2014-09-01

The onset of psychosis is usually preceded by psychotic experiences (PE). Little is known about the etiology of PE and whether the degree of genetic and environmental influences varies across different levels of severity. A recognized challenge is to identify individuals at high risk of developing psychotic disorders prior to disease onset. To investigate the degree of genetic and environmental influences on specific PE, assessed dimensionally, in adolescents in the community and in those who have many, frequent experiences (defined using quantitative cutoffs). We also assessed the degree of overlap in etiological influences between specific PE. Structural equation model-fitting, including univariate and bivariate twin models, liability threshold models, DeFries-Fulker extremes analysis, and the Cherny method, was used to analyze a representative community sample of 5059 adolescent twin pairs (mean [SD] age, 16.31 [0.68] years) from England and Wales. Psychotic experiences assessed as quantitative traits (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, and anhedonia, as well as parent-rated negative symptoms). Genetic influences were apparent for all PE (15%-59%), with modest shared environment for hallucinations and negative symptoms (17%-24%) and significant nonshared environment (49%-64%) for the self-rated scales and 17% for parent-rated negative symptoms. Three empirical approaches converged to suggest that the etiology in extreme-scoring groups (most extreme scoring: 5%, 10%, and 15%) did not differ significantly from that of the whole distribution. There was no linear change in heritability across the distribution of PE, with the exception of a modest increase in heritability for increasing severity of parent-rated negative symptoms. Of the PE that showed covariation, this appeared to be due to shared genetic influences (bivariate heritabilities, 0.54-0.71). These findings are consistent with the concept of a psychosis continuum, suggesting that the same genetic and environmental factors influence both extreme, frequent PE and milder, less frequent manifestations in adolescents. Individual PE in adolescence, assessed quantitatively, have lower heritability estimates and higher estimates of nonshared environment than those for the liability to schizophrenia. Heritability varies by type of PE, being highest for paranoia and parent-rated negative symptoms and lowest for hallucinations.

Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: A twin study of specific psychotic experiences in adolescence

PubMed Central

Zavos, Helena M.S.; Freeman, Daniel; Haworth, Claire M. A.; McGuire, Philip; Plomin, Robert; Cardno, Alastair G.; Ronald, Angelica

2014-01-01

Context The onset of psychosis is usually preceded by psychotic experiences, but little is known about their causes. The present study investigated the degree of genetic and environmental influences on specific psychotic experiences, assessed dimensionally, in adolescence in the community and in individuals with many, frequent experiences (defined using quantitative cut-offs). The degree of overlap in etiological influences between specific psychotic experiences was also investigated Objective Investigate degree of genetic and environmental influences on specific psychotic experiences, assessed dimensionally, in adolescence in the community and in individuals having many, frequent experiences (defined using quantitative cut-offs). Test degree of overlap in etiological influences between specific psychotic experiences. Design Classic twin design. Structural equation model-fitting. Univariate and bivariate twin models, liability threshold models, DeFries-Fulker extremes analysis and the Cherny Method. Setting Representative community sample of twins from England and Wales. Participants 5059 adolescent twin pairs (Mean age: 16.31 yrs, SD: 0.68 yrs). Main outcome measure Psychotic experiences assessed as quantitative traits (self-rated paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia; parent-rated negative symptoms). Results Genetic influences were apparent for all psychotic experiences (15-59%) with modest shared environment for hallucinations and negative symptoms (17-24%) and significant nonshared environment (49-64% for the self-rated scales, 17% for Parent-rated Negative Symptoms). Three different empirical approaches converged to suggest that the etiology in extreme groups (most extreme-scoring 5%, 10% and 15%) did not differ significantly from that of the whole distribution. There was no linear change in the heritability across the distribution of psychotic experiences, with the exception of a modest increase in heritability for increasing severity of parent-rated negative symptoms. Of the psychotic experiences that showed covariation, this appeared to be due to shared genetic influences (bivariate heritabilities = .54-.71). Conclusions and Relevance These findings are consistent with the concept of a psychosis continuum, suggesting that the same genetic and environmental factors influence both extreme, frequent psychotic experiences and milder, less frequent manifestations in adolescents. Individual psychotic experiences in adolescence, assessed quantitatively, have lower heritability estimates and higher estimates of nonshared environment than those for the liability to schizophrenia. Heritability varies by type of psychotic experience, being highest for paranoia and parent-rated negative symptoms, and lowest for hallucinations. PMID:25075799

Hospital law: the changing scene.

PubMed

Hirsh, H L

1978-01-01

The liability of hospitals in tort law has been a fairly recent development. Formerly, hospitals were protected from liability under the doctrine of charitable immunity. Legal "immunity" avoids liability in tort essentially under all circumstances. It is conferred not because of the particular facts of the situation but because of the status or position of the favored defendant. It does not deny the tort, merely the resulting liability. Such immunity does not mean that conduct that would amount to a tort on the part of other defendants is not still equally tortious in character, but merely that for the protection of the particular defendant, or of the interests which he represents, he is given absolution from liability. Similarly, the "captain-of-the-ship" and the attendant "borrowed or lent servant" doctrine is being abandoned. As medical technology continues to advance, the modern hospital will undoubtedly assume a greater responsibility toward its patients--with amplified medical-legal implications. The hospital is no longer a hotel where patients stay, awaiting treatment by their private physicians. The theory that the hospital does not act through its employees--physicians, nurses, and others--no longer reflects the trend in judicial philosophy. The decisions cited reflect the current trend in judicial analysis and thinking. Medical science has provided numerous benefits to humankind, but along with those benefits, numerous risks have accrued. Whether hospitals should have to bear the responsibilities inherent in such risks is a much-argued matter. However, hospital liability, in fact, is the trend of our judicial determination. The ramifications of this trend have been many. Hospitals and physicians will closely scrutinize surgical operations and other hospitals procedures and practices. The fact remains clear that responsibility for every patient is now shared by both the physicians and the hospital--share and share alike. The present thinking is that the liabilities can be minimized, without shifting the duties, obligations, and responsibilities, through risk management. Prevention, as always, is the best cure.

7 CFR 1944.405 - Authorized use of grant funds.

Code of Federal Regulations, 2011 CFR

2011-01-01

...'s Compensation, employer's share of social security, health benefits, and a reasonable tax deferred... as hammers and handsaws. (f) Payment of liability insurance and special purpose audit costs... general liability insurance cost and the cost of audits for the organization are generally indirect costs...

Back-neck pain and symptoms of anxiety and depression: a population-based twin study.

PubMed

Reichborn-Kjennerud, T; Stoltenberg, C; Tambs, K; Roysamb, E; Kringlen, E; Torgersen, S; Harris, J R

2002-08-01

Clinical and epidemiological studies have shown an association between anxiety and depression and pain in the back and neck. The nature of this relationship is not clear. This study aimed to investigate the extent to which common genetic and environmental aetiological factors contribute to the covariance between symptoms of anxiety and depression and back-neck pain. Measures of back-neck pain and symptoms of anxiety and depression were part of a self-report questionnaire sent in 1992 to twins born in Norway between 1967 and 1974 (3996 pairs). Structural equation modelling was applied to determine to what extent back-neck pain and symptoms of anxiety and depression share genetic and environmental liability factors. The phenotypic correlation between symptoms of anxiety and depression and back-neck pain was 0.31. Individual differences in both anxiety and depression and back-neck pain were best accounted for by additive genetic and individual environmental factors. Heritability estimates were 0.53 and 0.30 respectively. For back-neck pain, however, a model specifying only shared- and individual environmental effects could not be rejected. Bivariate analyses revealed that the correlation between back-neck pain and symptoms of anxiety and depression was best explained by additive genetic and individual environmental factors. Genetic factors affecting both phenotypes accounted for 60% of the covariation. There were no significant sex differences. The results support previous findings of a moderate association between back-neck pain and symptoms of anxiety and depression, and suggest that this association is primarily due to common genetic effects.

FEMALE AND MALE GENETIC EFFECTS ON OFFSPRING PATERNITY: ADDITIVE GENETIC (CO)VARIANCES IN FEMALE EXTRA-PAIR REPRODUCTION AND MALE PATERNITY SUCCESS IN SONG SPARROWS (MELOSPIZA MELODIA)

PubMed Central

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Losdat, Sylvain

2014-01-01

Ongoing evolution of polyandry, and consequent extra-pair reproduction in socially monogamous systems, is hypothesized to be facilitated by indirect selection stemming from cross-sex genetic covariances with components of male fitness. Specifically, polyandry is hypothesized to create positive genetic covariance with male paternity success due to inevitable assortative reproduction, driving ongoing coevolution. However, it remains unclear whether such covariances could or do emerge within complex polyandrous systems. First, we illustrate that genetic covariances between female extra-pair reproduction and male within-pair paternity success might be constrained in socially monogamous systems where female and male additive genetic effects can have opposing impacts on the paternity of jointly reared offspring. Second, we demonstrate nonzero additive genetic variance in female liability for extra-pair reproduction and male liability for within-pair paternity success, modeled as direct and associative genetic effects on offspring paternity, respectively, in free-living song sparrows (Melospiza melodia). The posterior mean additive genetic covariance between these liabilities was slightly positive, but the credible interval was wide and overlapped zero. Therefore, although substantial total additive genetic variance exists, the hypothesis that ongoing evolution of female extra-pair reproduction is facilitated by genetic covariance with male within-pair paternity success cannot yet be definitively supported or rejected either conceptually or empirically. PMID:24724612

Social risk or genetic liability for psychosis? A study of children born in Sweden and reared by adoptive parents.

PubMed

Wicks, Susanne; Hjern, Anders; Dalman, Christina

2010-10-01

Recent studies suggest a role for social factors during childhood in the later development of schizophrenia. Since social conditions in childhood are closely related to parental psychiatric illness, there is a need to disentangle how genes and social environmental factors interact. A total of 13,163 children born in Sweden between 1955 and 1984 and reared in Swedish adoptive families were linked to the National Patient Register until 2006 regarding admissions for non-affective psychoses, including schizophrenia. Hazard ratios for nonaffective psychoses were estimated in relation to three indicators of socioeconomic position in childhood (household data of the rearing family obtained via linkage to the National Censuses of 1960-1985) and in relation to indicator of genetic liability (biological parental inpatient care for psychosis). In addition, the total Swedish-born population was investigated. Increased risks for nonaffective psychosis were found among adoptees (without biological parental history of psychosis) reared in families with disadvantaged socioeconomic position, which consisted of adoptive parental unemployment (hazard ratio=2.0), single-parent household (hazard ratio=1.2), and living in apartments (hazard ratio=1.3). The risk was also increased among persons with genetic liability for psychosis alone (hazard ratio=4.7). Among those exposed to both genetic liability and a disadvantaged socioeconomic situation in childhood, the risk was considerably higher (hazard ratio=15.0, 10.3, and 5.7 for parental unemployment, single-parent household, and apartment living, respectively). Analyses in the larger population supported these results. The results indicate that children reared in families with a disadvantaged socioeconomic position have an increased risk for psychosis. There was also some support for an interaction effect, suggesting that social disadvantage increases this risk more in children with genetic liability for psychosis.

Staff Liability in Student Personnel Administration.

ERIC Educational Resources Information Center

Hammond, Edward H.

Student Personnel Administrators in institutions of postsecondary education share a common characteristic and experience a common fear related to their potential personal and institutional liability under the law for acts committed while carrying out their official duties. This article seeks to inform administrators of the parameters of the…

A Bivariate Genetic Analysis of Drug Abuse ascertained through medical and criminal registries in Swedish Twins, Siblings and Half-Siblings

PubMed Central

Maes, Hermine H.; Neale, Michael C.; Ohlsson, Henrik; Zahery, Mahsa; Lichtenstein, Paul; Sundquist, Kristina; Sundquist, Jan; Kendler, Kenneth S.

2016-01-01

Objective Using Swedish nationwide registry data, the authors investigated the correlation of genetic and environmental risk factors in the etiology of drug abuse as ascertained from medical and criminal registries by modeling twin and sibling data. Methods Medical drug abuse was defined using public inpatient and outpatient records, while criminal drug abuse was ascertained through legal records. Twin, full and half sibling pairs were obtained from the national twin and genealogical registers. Information about sibling pair residence within the same household was obtained from Statistics Sweden. Standard bivariate genetic structural equation modeling was applied to the population-based data on drug abuse ascertained through medical and crime registries, using OpenMx. Results Analyses of all possible pairs of twins (MZ: N=4,482; DZ: N=9,838 pairs), full- (N=1,278,086) and half-siblings (paternal: N=7,767; maternal N=70,553) who grew up together suggested that factors explaining familial resemblance for drug abuse as defined through medical or criminal registries were mostly the same. Results showed substantial heritability and moderate contributions of shared environmental factors to drug abuse; both were higher in males versus females, and higher for drug abuse ascertained through criminal than medical records. Because of the low prevalence of both assessments of drug abuse, having access to population data was crucial to obtain stable estimates. Conclusions Using objective registry data, the authors found that drug abuse - whether ascertained through medical versus criminal records - was highly heritable. Furthermore, shared environmental factors contributed significantly to the liability of drug abuse. Genetic and shared environmental risk factors for these two forms of drug abuse were highly correlated. PMID:27480873

A Bivariate Genetic Analysis of Drug Abuse Ascertained Through Medical and Criminal Registries in Swedish Twins, Siblings and Half-Siblings.

PubMed

Maes, Hermine H; Neale, Michael C; Ohlsson, Henrik; Zahery, Mahsa; Lichtenstein, Paul; Sundquist, Kristina; Sundquist, Jan; Kendler, Kenneth S

2016-11-01

Using Swedish nationwide registry data, the authors investigated the correlation of genetic and environmental risk factors in the etiology of drug abuse as ascertained from medical and criminal registries by modeling twin and sibling data. Medical drug abuse was defined using public inpatient and outpatient records, while criminal drug abuse was ascertained through legal records. Twin, full and half sibling pairs were obtained from the national twin and genealogical registers. Information about sibling pair residence within the same household was obtained from Statistics Sweden. Standard bivariate genetic structural equation modeling was applied to the population-based data on drug abuse ascertained through medical and crime registries, using OpenMx. Analyses of all possible pairs of twins (MZ: N = 4482; DZ: N = 9838 pairs), full- (N = 1,278,086) and half-siblings (paternal: N = 7767; maternal N = 70,553) who grew up together suggested that factors explaining familial resemblance for drug abuse as defined through medical or criminal registries were mostly the same. Results showed substantial heritability and moderate contributions of shared environmental factors to drug abuse; both were higher in males versus females, and higher for drug abuse ascertained through criminal than medical records. Because of the low prevalence of both assessments of drug abuse, having access to population data was crucial to obtain stable estimates. Using objective registry data, the authors found that drug abuse-whether ascertained through medical versus criminal records-was highly heritable. Furthermore, shared environmental factors contributed significantly to the liability of drug abuse. Genetic and shared environmental risk factors for these two forms of drug abuse were highly correlated.

Genetic testing in the workplace: the employer's coin toss.

PubMed

French, Samantha

2002-09-05

A toss of the coin by the modern-day employer reveals two options regarding genetic testing in the workplace. The employer may choose to take advantage of increasingly precise, available, and affordable genetic testing in order to ascertain the genetic characteristics--and deficiencies--of its employees. This outcome exposes the employer to a vast array of potential litigation and liability relating to the Americans with Disabilities Act, the Fourth Amendment, Title VII of the Civil Rights Act, and state legislation designed to protect genetic privacy. Alternatively, the employer may neglect to indulge in this trend of genetic testing and may face liability for employer negligence, violations of federal legislation such as OSHA regulations, and increased costs associated with insuring the health of genetically endangered employees. In the rapidly developing universe of genetic intelligence, the employer is faced with a staggering dilemma.

A better coefficient of determination for genetic profile analysis.

PubMed

Lee, Sang Hong; Goddard, Michael E; Wray, Naomi R; Visscher, Peter M

2012-04-01

Genome-wide association studies have facilitated the construction of risk predictors for disease from multiple Single Nucleotide Polymorphism markers. The ability of such "genetic profiles" to predict outcome is usually quantified in an independent data set. Coefficients of determination (R(2) ) have been a useful measure to quantify the goodness-of-fit of the genetic profile. Various pseudo-R(2) measures for binary responses have been proposed. However, there is no standard or consensus measure because the concept of residual variance is not easily defined on the observed probability scale. Unlike other nongenetic predictors such as environmental exposure, there is prior information on genetic predictors because for most traits there are estimates of the proportion of variation in risk in the population due to all genetic factors, the heritability. It is this useful ability to benchmark that makes the choice of a measure of goodness-of-fit in genetic profiling different from that of nongenetic predictors. In this study, we use a liability threshold model to establish the relationship between the observed probability scale and underlying liability scale in measuring R(2) for binary responses. We show that currently used R(2) measures are difficult to interpret, biased by ascertainment, and not comparable to heritability. We suggest a novel and globally standard measure of R(2) that is interpretable on the liability scale. Furthermore, even when using ascertained case-control studies that are typical in human disease studies, we can obtain an R(2) measure on the liability scale that can be compared directly to heritability. © 2012 Wiley Periodicals, Inc.

Female and male genetic effects on offspring paternity: additive genetic (co)variances in female extra-pair reproduction and male paternity success in song sparrows (Melospiza melodia).

PubMed

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Losdat, Sylvain

2014-08-01

Ongoing evolution of polyandry, and consequent extra-pair reproduction in socially monogamous systems, is hypothesized to be facilitated by indirect selection stemming from cross-sex genetic covariances with components of male fitness. Specifically, polyandry is hypothesized to create positive genetic covariance with male paternity success due to inevitable assortative reproduction, driving ongoing coevolution. However, it remains unclear whether such covariances could or do emerge within complex polyandrous systems. First, we illustrate that genetic covariances between female extra-pair reproduction and male within-pair paternity success might be constrained in socially monogamous systems where female and male additive genetic effects can have opposing impacts on the paternity of jointly reared offspring. Second, we demonstrate nonzero additive genetic variance in female liability for extra-pair reproduction and male liability for within-pair paternity success, modeled as direct and associative genetic effects on offspring paternity, respectively, in free-living song sparrows (Melospiza melodia). The posterior mean additive genetic covariance between these liabilities was slightly positive, but the credible interval was wide and overlapped zero. Therefore, although substantial total additive genetic variance exists, the hypothesis that ongoing evolution of female extra-pair reproduction is facilitated by genetic covariance with male within-pair paternity success cannot yet be definitively supported or rejected either conceptually or empirically. © 2014 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Genetics Home Reference: hereditary neuropathy with liability to pressure palsies

MedlinePlus

... PubMed Central Yilmaz U, Bird TT, Carter GT, Wang LH, Weiss MD. Pain in hereditary neuropathy with liability to pressure palsy: an association with fibromyalgia syndrome? Muscle Nerve. 2015 Mar;51(3):385-90. doi: 10.1002/ ...

High and low-risk specialties experience with the U.S. medical malpractice system

PubMed Central

2013-01-01

Background “High-liability risk specialties” tend to be the focus of medical malpractice system research and debate, but concerns and fears are not limited to this group. The objective of this study was to examine whether “high-liability risk” medical specialties have a different experience with the malpractice system than “low-liability risk” specialties. Methods We reviewed claims data from the Physician Insurers Association of America’s Data Sharing Project between January 1985 and December 2008. We used linear regression, controlling for year, to determine how liability risk affected outcomes of interest. Results In high-liability risk specialties, 33% of claims result in indemnity payments compared to 28% for low-liability risk specialties (p < 0.001). The average indemnity payment for high-liability risk specialties was $315,314 compared to $267,146 for low-liability risk specialties (p = 0.25). Although only a small percentage of claims go to trial, low-liability risk specialties have significantly more claims that are ultimately dropped, withdrawn or dismissed, while high-liability risk specialties have significantly more claims that result in plaintiff settlement (p < 0.001). Conclusions Malpractice risk exists for all specialties. Variability in indemnity costs are found in both high- and low-liability risk specialties. Differences in the reasons for which claims are initiated for high- and low-liability risk specialties likely necessitate different risk management solutions. PMID:24192524

Genetic and environmental influences on last-year major depression in adulthood: a highly heritable stable liability but strong environmental effects on 1-year prevalence.

PubMed

Kendler, K S; Gardner, C O

2017-07-01

This study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD). Our sample was 2153 members of female-female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves. The best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors. Both genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

Minimizing liability risks under the ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing.

PubMed

Evans, Barbara J

2013-12-01

Recent recommendations by the American College of Medical Genetics and Genomics (ACMG) for reporting incidental findings present novel ethical and legal issues. This article expresses no views on the ethical aspects of these recommendations and focuses strictly on liability risks and how to minimize them. The recommendations place labs and clinicians in a new liability environment that exposes them to intentional tort lawsuits as well to traditional suits for negligence. Intentional tort suits are especially troubling because of their potential to inflict ruinous personal financial losses on individual clinicians and laboratory personnel. This article surveys this new liability landscape and describes analytical approaches for minimizing tort liabilities. To a considerable degree, liability risks can be controlled by structuring activities in ways that make future lawsuits nonviable before the suits ever arise. Proactive liability analysis is an effective tool for minimizing tort liabilities in connection with the testing and reporting activities that the ACMG recommends.

Minimizing liability risks under the ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing

PubMed Central

Evans, Barbara J.

2014-01-01

Recent recommendations by the American College of Medical Genetics and Genomics (ACMG) for reporting incidental findings present novel ethical and legal issues. This article expresses no views on the ethical aspects of these recommendations and focuses strictly on liability risks and how to minimize them. The recommendations place labs and clinicians in a new liability environment that exposes them to intentional tort lawsuits as well to traditional suits for negligence. Intentional tort suits are especially troubling because of their potential to inflict ruinous personal financial losses on individual clinicians and laboratory personnel. This article surveys this new liability landscape and describes analytical approaches for minimizing tort liabilities. To a considerable degree, liability risks can be controlled by structuring activities in ways that make future lawsuits nonviable before the suits ever arise. Proactive liability analysis is an effective tool for minimizing tort liabilities in connection with the testing and reporting activities that the ACMG recommends. PMID:24030435

Evidence for a Heritable Brain Basis to Deviance-Promoting Deficits in Self-Control.

PubMed

Yancey, James R; Venables, Noah C; Hicks, Brian M; Patrick, Christopher J

2013-01-01

Classic criminological theories emphasize the role of impaired self-control in behavioral deviancy. Reduced amplitude of the P300 brain response is reliably observed in individuals with antisocial and substance-related problems, suggesting it may serve as a neurophysiological indicator of deficiencies in self-control that confer liability to deviancy. The current study evaluated the role of self-control capacity - operationalized by scores on a scale measure of trait disinhibition - in mediating the relationship between P300 brain response and behavioral deviancy in a sample of adult twins ( N =419) assessed for symptoms of antisocial/addictive disorders and P300 brain response. As predicted, greater disorder symptoms and higher trait disinhibition scores each predicted smaller P300 amplitude, and trait disinhibition mediated observed relations between antisocial/addictive disorders and P300 response. Further, twin modeling analyses revealed that trait disinhibition scores and disorder symptoms reflected a common genetic liability, and this genetic liability largely accounted for the observed phenotypic relationship between antisocial-addictive problems and P300 brain response. These results provide further evidence that heritable weaknesses in self-control capacity confer liability to antisocial/addictive outcomes and that P300 brain response indexes this dispositional liability.

Gene Expression Elucidates Functional Impact of Polygenic Risk for Schizophrenia

PubMed Central

Fromer, Menachem; Roussos, Panos; Sieberts, Solveig K; Johnson, Jessica S; Kavanagh, David H; Perumal, Thanneer M; Ruderfer, Douglas M; Oh, Edwin C; Topol, Aaron; Shah, Hardik R; Klei, Lambertus L; Kramer, Robin; Pinto, Dalila; Gümüş, Zeynep H; Cicek, A. Ercument; Dang, Kristen K; Browne, Andrew; Lu, Cong; Xie, Lu; Readhead, Ben; Stahl, Eli A; Parvizi, Mahsa; Hamamsy, Tymor; Fullard, John F; Wang, Ying-Chih; Mahajan, Milind C; Derry, Jonathan M J; Dudley, Joel; Hemby, Scott E; Logsdon, Benjamin A; Talbot, Konrad; Raj, Towfique; Bennett, David A; De Jager, Philip L; Zhu, Jun; Zhang, Bin; Sullivan, Patrick F; Chess, Andrew; Purcell, Shaun M; Shinobu, Leslie A; Mangravite, Lara M; Toyoshiba, Hiroyoshi; Gur, Raquel E; Hahn, Chang-Gyu; Lewis, David A; Haroutunian, Vahram; Peters, Mette A; Lipska, Barbara K; Buxbaum, Joseph D; Schadt, Eric E; Hirai, Keisuke; Roeder, Kathryn; Brennand, Kristen J; Katsanis, Nicholas; Domenici, Enrico; Devlin, Bernie; Sklar, Pamela

2016-01-01

Over 100 genetic loci harbor schizophrenia associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of schizophrenia cases (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ~20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3, or SNAP91. Altering expression of FURIN, TSNARE1, or CNTN4 changes neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yields abnormal migration. Of 693 genes showing significant case/control differential expression, their fold changes are ≤ 1.33, and an independent cohort yields similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases. PMID:27668389

Gene expression elucidates functional impact of polygenic risk for schizophrenia.

PubMed

Fromer, Menachem; Roussos, Panos; Sieberts, Solveig K; Johnson, Jessica S; Kavanagh, David H; Perumal, Thanneer M; Ruderfer, Douglas M; Oh, Edwin C; Topol, Aaron; Shah, Hardik R; Klei, Lambertus L; Kramer, Robin; Pinto, Dalila; Gümüş, Zeynep H; Cicek, A Ercument; Dang, Kristen K; Browne, Andrew; Lu, Cong; Xie, Lu; Readhead, Ben; Stahl, Eli A; Xiao, Jianqiu; Parvizi, Mahsa; Hamamsy, Tymor; Fullard, John F; Wang, Ying-Chih; Mahajan, Milind C; Derry, Jonathan M J; Dudley, Joel T; Hemby, Scott E; Logsdon, Benjamin A; Talbot, Konrad; Raj, Towfique; Bennett, David A; De Jager, Philip L; Zhu, Jun; Zhang, Bin; Sullivan, Patrick F; Chess, Andrew; Purcell, Shaun M; Shinobu, Leslie A; Mangravite, Lara M; Toyoshiba, Hiroyoshi; Gur, Raquel E; Hahn, Chang-Gyu; Lewis, David A; Haroutunian, Vahram; Peters, Mette A; Lipska, Barbara K; Buxbaum, Joseph D; Schadt, Eric E; Hirai, Keisuke; Roeder, Kathryn; Brennand, Kristen J; Katsanis, Nicholas; Domenici, Enrico; Devlin, Bernie; Sklar, Pamela

2016-11-01

Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of people with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ∼20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant case-versus-control differential expression, their fold changes were ≤ 1.33, and an independent cohort yielded similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases.

78 FR 23934 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-23

... limited liability company, individually, with Stephen L. LaFrance, Jr., Little Rock, Arkansas, as the sole manager, and LAF-GW and Stephen L. LaFrance, Jr., together as a group acting in concert with JSJ Properties, LLC, a Missouri limited liability company, with Stephen L. LaFrance, Jr., Jason P. LaFrance, and...

Genetic and environmental risk factors in adolescent substance use.

PubMed

Silberg, Judy; Rutter, Michael; D'Onofrio, Brian; Eaves, Lindon

2003-07-01

The present study was undertaken with the goal of understanding the causes of association between substance use and both conduct disturbance (CD) and depression in adolescent boys and girls. Multivariate genetic structural equation models were fitted to multi-informant, multi-wave, longitudinal data collected in extensive home interviews with parents and children with respect to 307 MZ male, 392 MZ female, 185 DZ male, and 187 DZ female, same-sex twin pairs aged 12-17 years from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). Although conduct disturbance and depression were moderately associated with substance use, the pattern of genetic and environmental risk differed for males and females and across the two disorders. Genetic factors were predominant in girls' substance use whereas boys' use was mediated primarily by shared environmental factors reflecting family dysfunction and deviant peers. The patterns of correlations across the two waves of the study were consistent with conduct disturbance leading to substance use in both males and females, but depression leading to smoking, drug use and, to a lesser extent, alcohol use in girls. The comorbidity between substance use and depression, and between substance use and conduct disturbance in childhood/adolescence, probably reflects rather different mediating mechanisms--as well as a different time frame, with conduct disturbance preceding substance use but depression following it. In both, the co-occurrence partially reflected a shared liability but, in girls, genetic influences played an important role in the comorbidity involving depression, whereas in both sexes (but especially in boys) environmental factors played a substantial role. The extent to which these differences reflect genuine differences in the causal mechanisms underlying substance use and CD/depression in boys and girls revealed in the present analysis awaits replication from studies of other general population samples.

A longitudinal twin and sibling study of the hopelessness theory of depression in adolescence and young adulthood.

PubMed

Waszczuk, M A; Coulson, A E; Gregory, A M; Eley, T C

2016-07-01

Maladaptive cognitive biases such as negative attributional style and hopelessness have been implicated in the development and maintenance of depression. According to the hopelessness theory of depression, hopelessness mediates the association between attributional style and depression. The aetiological processes underpinning this influential theory remain unknown. The current study investigated genetic and environmental influences on hopelessness and its concurrent and longitudinal associations with attributional style and depression across adolescence and emerging adulthood. Furthermore, given high co-morbidity between depression and anxiety, the study investigated whether these maladaptive cognitions constitute transdiagnostic cognitive content common to both internalizing symptoms. A total of 2619 twins/siblings reported attributional style (mean age 15 and 17 years), hopelessness (mean age 17 years), and depression and anxiety symptoms (mean age 17 and 20 years). Partial correlations revealed that attributional style and hopelessness were uniquely associated with depression but not anxiety symptoms. Hopelessness partially mediated the relationship between attributional style and depression. Hopelessness was moderately heritable (A = 0.37, 95% confidence interval 0.28-0.47), with remaining variance accounted for by non-shared environmental influences. Independent pathway models indicated that a set of common genetic influences largely accounted for the association between attributional style, hopelessness and depression symptoms, both concurrently and across development. The results provide novel evidence that associations between attributional style, hopelessness and depression symptoms are largely due to shared genetic liability, suggesting developmentally stable biological pathways underpinning the hopelessness theory of depression. Both attributional style and hopelessness constituted unique cognitive content in depression. The results inform molecular genetics research and cognitive treatment approaches.

Heritability of the Number of Teeth in Middle-Aged and Older Danish Twins.

PubMed

Kurushima, Y; Silventoinen, K; Dokkedal, U; Skytthe, A; Mucci, L A; Christensen, K; Hjelmborg, J V B

2017-12-01

Tooth loss is a common health concern in older adults. We aimed to estimate the relative contributions of genetic and environmental factors to the variation in the number of teeth in middle-aged and older populations using a population-based cohort of Danish twins. The study included 5,269 Danish middle-aged or older twins who provided data on the number of teeth at baseline by structured interviews. The data were analyzed using univariate liability threshold modeling, stratified by sex and age, to estimate familial risk of tooth loss as well as estimates of heritability. In the whole cohorts, 23% of participants were edentate and 53% had retained 20 or more teeth. A statistical model including additive genetic factors and environmental factors partly shared by co-twins and partly unique to each individual twin gave the best statistical fit for the number of teeth in both age categories as well as in men and women. Overall, additive genetic factors explained 36% (95% confidence interval [CI]: 23% to 49%), common environmental factors 20% (95% CI: 9% to 31%), and unique environmental factors 44% (95% CI: 40% to 48%) of the total variation of the number of teeth. This study indicates that a substantial part of the variation in tooth loss is explained by genetic as well as environmental factors shared by co-twins. Our results implied that family background importantly affects tooth loss in both the middle-aged and the older populations. Family history is thus an important factor to take into account in dental health care.

Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

PubMed Central

Wiste, Anna; Robinson, Elise B; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C; Fitzmaurice, Garrett M; Rietschel, Marcella; Penninx, Brenda W; Smoller, Jordan W; Perlis, Roy H

2014-01-01

Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of this study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European–American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts. Results A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04). Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ≤ 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8–1.1%. However, analyses in two replication cohorts testing a five feature model did not support this association. Conclusions Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, results are at most inconclusive because of lack of replication. Replication efforts are challenged by different ascertainment and assessment strategies in the different cohorts. The methodological approach described here may prove useful in applying genetic data to clarify psychiatric nosology in future studies. PMID:24725193

A Children of Twins Study of parental divorce and offspring psychopathology.

PubMed

D'Onofrio, Brian M; Turkheimer, Eric; Emery, Robert E; Maes, Hermine H; Silberg, Judy; Eaves, Lindon J

2007-07-01

Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed.

Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families.

PubMed

Page, Joshua; Constantino, John Nicholas; Zambrana, Katherine; Martin, Eden; Tunc, Ilker; Zhang, Yi; Abbacchi, Anna; Messinger, Daniel

2016-01-01

Recent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations-the present study explored these phenomena in a well-characterized Hispanic population. The present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers. In families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations. Quantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs-the magnitude of which may vary across cultures-constitutes a mechanism by which background genetic liability for ASD can accumulate in a given family in successive generations.

31 CFR 50.93 - Application of pro rata share.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Application of pro rata share. 50.93 Section 50.93 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM Cap on Annual Liability § 50.93 Application of pro rata share. An insurer shall apply the PRLP to...

26 CFR 1.1502-3 - Consolidated tax credits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... share of the consolidated net income tax minus 25 percent of the quantity which is equal to so much of... consolidated return year is limited to: (a) So much of the consolidated liability for tax as does not exceed... equals the member's share of the consolidated net income tax minus the member's share of the consolidated...

Evidence for a Heritable Brain Basis to Deviance-Promoting Deficits in Self-Control

PubMed Central

Yancey, James R.; Venables, Noah C.; Hicks, Brian M.; Patrick, Christopher J.

2013-01-01

Purpose Classic criminological theories emphasize the role of impaired self-control in behavioral deviancy. Reduced amplitude of the P300 brain response is reliably observed in individuals with antisocial and substance-related problems, suggesting it may serve as a neurophysiological indicator of deficiencies in self-control that confer liability to deviancy. Methods The current study evaluated the role of self-control capacity — operationalized by scores on a scale measure of trait disinhibition — in mediating the relationship between P300 brain response and behavioral deviancy in a sample of adult twins (N=419) assessed for symptoms of antisocial/addictive disorders and P300 brain response. Results As predicted, greater disorder symptoms and higher trait disinhibition scores each predicted smaller P300 amplitude, and trait disinhibition mediated observed relations between antisocial/addictive disorders and P300 response. Further, twin modeling analyses revealed that trait disinhibition scores and disorder symptoms reflected a common genetic liability, and this genetic liability largely accounted for the observed phenotypic relationship between antisocial-addictive problems and P300 brain response. Conclusions These results provide further evidence that heritable weaknesses in self-control capacity confer liability to antisocial/addictive outcomes and that P300 brain response indexes this dispositional liability. PMID:24187392

Genetic and environmental influences on non-specific neck pain in early adolescence: A classical twin study

PubMed Central

Ståhl, Minna K; El-Metwally, Ashraf A; Mikkelsson, Marja K; Salminen, Jouko J; Pulkkinen, Lea R; Rose, Richard J; Kaprio, Jaakko A

2012-01-01

Background Prevalence of neck pain has increased among adolescents. The origins of adult chronic neck pain may lie in late childhood, but for early prevention, more information is needed about its aetiology. We investigated the relative roles of genetic and environmental factors in early adolescent neck pain with a classic twin study. Methods Frequency of neck pain was assessed with a validated pain questionnaire in a population-based sample of nearly 1800 pairs of 11–12-year-old Finnish twins. Twin pair similarity for neck pain was quantified by polychoric correlations, and variance components were estimated with biometric structural equation modelling. Results Prevalence of neck pain reported at least once monthly was 38% and at least once weekly 16%, with no significant differences between gender or zygosity. A greater polychoric correlation in liability to neck pain was found in monozygotic (0.67) than for dizygotic pairs (0.38), suggesting strong genetic influences. Model-fitting indicated that 68% (95% CI 62 to 74) of the variation in liability to neck pain could be attributed to genetic effects, with the remainder attributed to unshared environmental effects. No evidence for sex-specific genetic effects or for sex differences in the magnitude of genetic effects was found. Conclusions Genetic and unique environmental factors seem to play the most important roles in liability to neck pain in early adolescence. Future research should be directed to identifying pathways for genetic influences on neck pain and in exploring effectiveness of interventions that target already identified environmental risk factors. PMID:23139100

Chronic Inflammatory Demyelinating Polyneuropathy Manifesting as Neuropathy With Liability to Pressure Palsies: A Case Report.

PubMed

Shah, Akshay; Rison, Richard A; Beydoun, Said R

2015-12-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive demyelinating neuropathy, which typically presents with proximal and distal neuropathic symptoms and is typically responsive to immunomodulatory therapies. Many variants have been subsequently described in the literature and have similarly shown to be responsive to immunotherapy. We present a case of a 43-year-old Middle Eastern/Arabic man presenting with symptoms of mixed sensorimotor neuropathy most evident at entrapment sites mimicking hereditary neuropathy with liability to pressure palsies. His electrodiagnostic study revealed features of acquired demyelinating neuropathy and a negative genetic workup. Alternative diagnosis of CIDP was considered in the context of symptomatic disease progression, negative genetic workup, and electrodiagnosis leading to initiation of immunotherapy with intravenous immunoglobulins. His neuropathy responded confirming our diagnosis of an inflammatory demyelinating polyneuropathy. We describe a previously unknown variant of CIDP with phenotypic characteristics of hereditary neuropathy with liability to pressure palsies and its potential for successful treatment with intravenous immunoglobulins. This case illustrates an unusual presentation of CIDP mimicking hereditary neuropathy with liability to pressure palsies.

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

PubMed

Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M; Culverhouse, Robert C; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N; Maher, Brion S; Melroy, Whitney E; Nelson, Elliot C; Reid, Mark W; Robinson, Jason D; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A; Cannon, Dale S; Cichon, Sven; Corley, Robin P; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J; Grucza, Richard A; Hardin, Jill; Hartmann, Annette M; Heath, Andrew C; Herms, Stefan; Hodgkinson, Colin A; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O; Johnstone, Elaine; Kaneva, Radka P; Kendler, Kenneth S; Kiefer, Falk; Kranzler, Henry R; Krauter, Ken S; Levran, Orna; Lucae, Susanne; Lynskey, Michael T; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G; Mattheisen, Manuel; Montgomery, Grant W; Müller-Myhsok, Bertram; Murphy, Michael F; Neale, Michael C; Nikolov, Momchil A; Nishita, Denise; Nöthen, Markus M; Nurnberger, John; Partonen, Timo; Pergadia, Michele L; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wall, Tamara L; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W; Chen, Jingchun; Cinciripini, Paul M; Edenberg, Howard J; Ehringer, Marissa A; Ferrell, Robert E; Gelernter, Joel; Goldman, David; Hewitt, John K; Hopfer, Christian J; Iacono, William G; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M; Madden, Pamela A F; McGue, Matt; Munafò, Marcus R; Philibert, Robert A; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T; Swan, Gary E; Todorov, Alexandre A; Vanyukov, Michael M; Weiss, Robert B; Bierut, Laura J; Saccone, Nancy L

2016-03-01

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.

Association of the OPRM1 variant rs1799971 (A118G) with non-specific liability to substance dependence in a collaborative de novo meta-analysis of European-ancestry cohorts

PubMed Central

Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M.; Culverhouse, Robert C.; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M.; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N.; Maher, Brion S.; Melroy, Whitney E.; Nelson, Elliot C.; Reid, Mark W.; Robinson, Jason D.; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A.; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A.; Cannon, Dale S.; Cichon, Sven; Corley, Robin P.; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J.; Grucza, Richard A.; Hardin, Jill; Hartmann, Annette M.; Heath, Andrew C.; Herms, Stefan; Hodgkinson, Colin A.; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O.; Johnstone, Elaine; Kaneva, Radka P.; Kendler, Kenneth S.; Kiefer, Falk; Kranzler, Henry R.; Krauter, Ken S.; Levran, Orna; Lucae, Susanne; Lynskey, Michael T.; Maier, Wolfgang; Mann, Karl; Martin, Nicholas G.; Mattheisen, Manuel; Montgomery, Grant W.; Müller-Myhsok, Bertram; Murphy, Michael F.; Neale, Michael C.; Nikolov, Momchil A.; Nishita, Denise; Nöthen, Markus M; Nurnberger, John; Partonen, Timo; Pergadia, Michele L.; Reynolds, Maureen; Ridinger, Monika; Rose, Richard J.; Rouvinen-Lagerström, Noora; Scherbaum, Norbert; Schmäl, Christine; Soyka, Michael; Stallings, Michael C.; Steffens, Michael; Treutlein, Jens; Tsuang, Ming; Wall, Tamara L.; Wodarz, Norbert; Yuferov, Vadim; Zill, Peter; Bergen, Andrew W.; Chen, Jingchun; Cinciripini, Paul M.; Edenberg, Howard J; Ehringer, Marissa A.; Ferrell, Robert E.; Gelernter, Joel; Goldman, David; Hewitt, John K.; Hopfer, Christian J.; Iacono, William G.; Kaprio, Jaakko; Kreek, Mary Jeanne; Kremensky, Ivo M.; Madden, Pamela A.F.; McGue, Matt; Munafò, Marcus R.; Philibert, Robert A.; Rietschel, Marcella; Roy, Alec; Rujescu, Dan; Saarikoski, Sirkku T.; Swan, Gary E.; Todorov, Alexandre A.; Vanyukov, Michael M.; Weiss, Robert B.; Bierut, Laura J.; Saccone, Nancy L.

2015-01-01

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for “general” substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day > 20 versus ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83–0.97], p-value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses. PMID:26392368

Is an Early Age at Illness Onset in Schizophrenia Associated With Increased Genetic Susceptibility? Analysis of Data From the Nationwide Danish Twin Register.

PubMed

Hilker, Rikke; Helenius, Dorte; Fagerlund, Birgitte; Skytthe, Axel; Christensen, Kaare; Werge, Thomas M; Nordentoft, Merete; Glenthøj, Birte

2017-04-01

Early age at illness onset has been viewed as an important liability marker for schizophrenia, which may be associated with an increased genetic vulnerability. A twin approach can be valuable, because it allows for the investigation of specific illness markers in individuals with a shared genetic background. We linked nationwide registers to identify a cohort of twin pairs born in Denmark from 1951 to 2000 (N=31,524 pairs), where one or both twins had a diagnosis in the schizophrenia spectrum. We defined two groups consisting of; N=788 twin pairs (affected with schizophrenia spectrum) and a subsample of N=448 (affected with schizophrenia). Survival analysis was applied to investigate the effect of age at illness onset. We found that early age at illness onset compared to later onset in the first diagnosed twin can be considered a major risk factor for developing schizophrenia in the second twin. Additionally, we found that the stronger genetic component in MZ twins compared to DZ twins is manifested in the proximity of assigned diagnosis within pairs. Early onset schizophrenia could be linked to a more severe genetic predisposition, indicating that age might be perceived as a clinical marker for genetic vulnerability for the illness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Coexistence or Conflict? A European Perspective on GMOs and the Problem of Liability

ERIC Educational Resources Information Center

Rodgers, Christopher P.

2007-01-01

In March 2004, the U.K. government announced its intention to grant limited authorization for the growing of commercial genetically modified (GM) crops. This article reviews the potential liabilities that may arise from GM cropping, for environmental damage and for economic losses claimed by non-GM producers. It considers the application of the…

Genetic evaluation of mastitis liability and recovery through longitudinal analysis of transition probabilities

PubMed Central

2012-01-01

Background Many methods for the genetic analysis of mastitis use a cross-sectional approach, which omits information on, e.g., repeated mastitis cases during lactation, somatic cell count fluctuations, and recovery process. Acknowledging the dynamic behavior of mastitis during lactation and taking into account that there is more than one binary response variable to consider, can enhance the genetic evaluation of mastitis. Methods Genetic evaluation of mastitis was carried out by modeling the dynamic nature of somatic cell count (SCC) within the lactation. The SCC patterns were captured by modeling transition probabilities between assumed states of mastitis and non-mastitis. A widely dispersed SCC pattern generates high transition probabilities between states and vice versa. This method can model transitions to and from states of infection simultaneously, i.e. both the mastitis liability and the recovery process are considered. A multilevel discrete time survival model was applied to estimate breeding values on simulated data with different dataset sizes, mastitis frequencies, and genetic correlations. Results Correlations between estimated and simulated breeding values showed that the estimated accuracies for mastitis liability were similar to those from previously tested methods that used data of confirmed mastitis cases, while our results were based on SCC as an indicator of mastitis. In addition, unlike the other methods, our method also generates breeding values for the recovery process. Conclusions The developed method provides an effective tool for the genetic evaluation of mastitis when considering the whole disease course and will contribute to improving the genetic evaluation of udder health. PMID:22475575

26 CFR 1.752-3 - Partner's share of nonrecourse liabilities.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Provisions Common to Part II, Subchapter K, Chapter 1 of... this section as follows— (1) The partner's share of partnership minimum gain determined in accordance with the rules of section 704(b) and the regulations thereunder; (2) The amount of any taxable gain...

26 CFR 1.752-3 - Partner's share of nonrecourse liabilities.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Provisions Common to Part II, Subchapter K, Chapter 1 of... this section as follows— (1) The partner's share of partnership minimum gain determined in accordance with the rules of section 704(b) and the regulations thereunder; (2) The amount of any taxable gain...

26 CFR 1.752-3 - Partner's share of nonrecourse liabilities.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Provisions Common to Part II, Subchapter K, Chapter 1 of... this section as follows— (1) The partner's share of partnership minimum gain determined in accordance with the rules of section 704(b) and the regulations thereunder; (2) The amount of any taxable gain...

26 CFR 1.752-3 - Partner's share of nonrecourse liabilities.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Provisions Common to Part II, Subchapter K, Chapter 1 of... this section as follows— (1) The partner's share of partnership minimum gain determined in accordance with the rules of section 704(b) and the regulations thereunder; (2) The amount of any taxable gain...

Liability: the complicated task of licensing law enforcement technologies

NASA Astrophysics Data System (ADS)

Hops, Larry W.; Overlin, Trudy K.

1997-01-01

This paper discusses a situation where a company (licensor) requires a liability policy as a condition of a license agreement, when licensing law enforcement technologies. The purpose of this discussion is to evaluate the reasons behind the need for extensive liability policies to protect licensors when marketing their law enforcement technologies to private industry. Finding a solution to the problem, therefore reducing the potential for high liability insurance costs, would be desirable. Since the risks associated with most technologies are virtually unknown, and because such technologies are used in very unpredictable legal environments, alternative ways of guaranteeing research and development enterprises that they will be covered against product liability are needed. Without such protection, licensors may require licensees to indemnify them beyond the usual guarantees provided in a licensing agreement, which may make the license too costly for smaller businesses. When the share of the market is limited to larger corporations, competition suffers and ultimately the cost to law enforcement agencies increases.

Prenatal Genetic Testing Chart

MedlinePlus

... www.acog.org/Patients/FAQs/Prenatal-Genetic-Diagnostic-Tests › › Resources & Publications Committee Opinions Practice Bulletins Patient Education Green Journal Clinical Updates Practice Management Coding Health Info Technology Professional Liability Managing Your Practice Patient Safety & Quality ...

Heritability of tic disorders: a twin-family study.

PubMed

Zilhão, N R; Olthof, M C; Smit, D J A; Cath, D C; Ligthart, L; Mathews, C A; Delucchi, K; Boomsma, D I; Dolan, C V

2017-04-01

Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects. Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.

A Children of Twins Study of parental divorce and offspring psychopathology

PubMed Central

D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Maes, Hermine H.; Silberg, Judy; Eaves, Lindon J.

2010-01-01

Background Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. Method We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. Results The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. Conclusions The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed. PMID:17593147

Theory of mind network activity is altered in subjects with familial liability for schizophrenia

PubMed Central

Mohnke, Sebastian; Erk, Susanne; Schnell, Knut; Romanczuk-Seiferth, Nina; Schmierer, Phöbe; Romund, Lydia; Garbusow, Maria; Wackerhagen, Carolin; Ripke, Stephan; Grimm, Oliver; Haller, Leila; Witt, Stephanie H.; Degenhardt, Franziska; Tost, Heike; Heinz, Andreas; Meyer-Lindenberg, Andreas; Walter, Henrik

2016-01-01

As evidenced by a multitude of studies, abnormalities in Theory of Mind (ToM) and its neural processing might constitute an intermediate phenotype of schizophrenia. If so, neural alterations during ToM should be observable in unaffected relatives of patients as well, since they share a considerable amount of genetic risk. While behaviorally, impaired ToM function is confirmed meta-analytically in relatives, evidence on aberrant function of the neural ToM network is sparse and inconclusive. The present study therefore aimed to further explore the neural correlates of ToM in relatives of schizophrenia. About 297 controls and 63 unaffected first-degree relatives of patients with schizophrenia performed a ToM task during functional magnetic resonance imaging. Consistent with the literature relatives exhibited decreased activity of the medial prefrontal cortex. Additionally, increased recruitment of the right middle temporal gyrus and posterior cingulate cortex was found, which was related to subclinical paranoid symptoms in relatives. These results further support decreased medial prefrontal activation during ToM as an intermediate phenotype of genetic risk for schizophrenia. Enhanced recruitment of posterior ToM areas in relatives might indicate inefficiency mechanisms in the presence of genetic risk. PMID:26341902

The Legal Past, Present and Future of Prenatal Genetic Testing: Professional Liability and Other Legal Challenges Affecting Patient Access to Services.

PubMed

Pergament, Deborah; Ilijic, Katie

2014-12-15

This chapter is an overview of the current status of the law in the United States regarding prenatal genetic testing with an emphasis on issues related to professional liability and other challenges affecting patient access to prenatal genetic testing. The chapter discusses the roles that federal regulations, promulgated by the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), play in the regulation of prenatal genetic tests. The chapter discusses tort litigation based on allegations of malpractice in the provision of prenatal genetic testing and how courts have analyzed issues related to causation, damages and mitigation of damages. The chapter provides reference information regarding how individual states address causes of action under the tort theories of wrongful birth and wrongful life. The chapter concludes with a discussion of future legal issues that may affect clinical prenatal genetic testing services arising from the continued expansion of prenatal genetic testing, legal restrictions on access to abortion and the potential development of embryonic treatments.

The Legal Past, Present and Future of Prenatal Genetic Testing: Professional Liability and Other Legal Challenges Affecting Patient Access to Services

PubMed Central

Pergament, Deborah; Ilijic, Katie

2014-01-01

This chapter is an overview of the current status of the law in the United States regarding prenatal genetic testing with an emphasis on issues related to professional liability and other challenges affecting patient access to prenatal genetic testing. The chapter discusses the roles that federal regulations, promulgated by the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), play in the regulation of prenatal genetic tests. The chapter discusses tort litigation based on allegations of malpractice in the provision of prenatal genetic testing and how courts have analyzed issues related to causation, damages and mitigation of damages. The chapter provides reference information regarding how individual states address causes of action under the tort theories of wrongful birth and wrongful life. The chapter concludes with a discussion of future legal issues that may affect clinical prenatal genetic testing services arising from the continued expansion of prenatal genetic testing, legal restrictions on access to abortion and the potential development of embryonic treatments. PMID:26237611

The Legal Doctrine on 'Limitation of Liability' in the Precedent Analysis on Plastic Surgery Medical Malpractice Lawsuits.

PubMed

Park, Bo Young; Pak, Ji-Hyun; Hong, Seung-Eun; Kang, So Ra

2015-12-01

This study intended to review the precedents on plastic surgery medical malpractice lawsuits in lower-court trials, classify the reasons of 'limitation of liability' by type, and suggest a standard in the acknowledgement of limitation of liability ratio. The 30 lower-court's rulings on the cases bearing the medical negligence of the defendants acknowledged the liability ratio of the defendants between 30% and 100%. Ten cases ruled that the defendants were wholly responsible for the negligence or malpractice, while 20 cases acknowledged the limitation of liability principle. In the determination of damage compensation amount, the court considered the cause of the victim side, which contributed in the occurrence of the damage. The court also believed that it is against the idea of fairness to have the assailant pay the whole compensation, even there is no victim-side cause such as previous illness or physical constitution of the patient, and applies the legal doctrine on limitation of liability, which is an independent damage compensation adjustment system. Most of the rulings also limited the ratio of responsibility to certain extent. When considering that the legal doctrine on limitation of liability which supports concrete validity for the fair sharing of damage, the tangible classification of causes of limitation of liability suggested in this study would be a useful tool in forecasting the ruling of a plastic surgery medical malpractice lawsuit.

The Legal Doctrine on 'Limitation of Liability' in the Precedent Analysis on Plastic Surgery Medical Malpractice Lawsuits

PubMed Central

Kang, So Ra

2015-01-01

This study intended to review the precedents on plastic surgery medical malpractice lawsuits in lower-court trials, classify the reasons of 'limitation of liability' by type, and suggest a standard in the acknowledgement of limitation of liability ratio. The 30 lower-court's rulings on the cases bearing the medical negligence of the defendants acknowledged the liability ratio of the defendants between 30% and 100%. Ten cases ruled that the defendants were wholly responsible for the negligence or malpractice, while 20 cases acknowledged the limitation of liability principle. In the determination of damage compensation amount, the court considered the cause of the victim side, which contributed in the occurrence of the damage. The court also believed that it is against the idea of fairness to have the assailant pay the whole compensation, even there is no victim-side cause such as previous illness or physical constitution of the patient, and applies the legal doctrine on limitation of liability, which is an independent damage compensation adjustment system. Most of the rulings also limited the ratio of responsibility to certain extent. When considering that the legal doctrine on limitation of liability which supports concrete validity for the fair sharing of damage, the tangible classification of causes of limitation of liability suggested in this study would be a useful tool in forecasting the ruling of a plastic surgery medical malpractice lawsuit. PMID:26713045

Common Gene Variants Account for Most Genetic Risk for Autism

MedlinePlus

... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study. The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations ...

Liability concerns and shared use of school recreational facilities in underserved communities.

PubMed

Spengler, John O; Connaughton, Daniel P; Maddock, Jason E

2011-10-01

In underserved communities, schools can provide the physical structure and facilities for informal and formal recreation as well as after-school, weekend, and summer programming. The importance of community access to schools is acknowledged by authoritative groups; however, fear of liability is believed to be a key barrier to community access. The purpose of this study was to investigate perceptions of liability risk and associated issues among school administrators in underserved communities. A national survey of school administrators in underserved communities (n=360, response rate of 21%) was conducted in 2009 and analyzed in 2010. Liability perceptions in the context of community access were assessed through descriptive statistics. The majority of respondents (82.2%) indicated concern for liability should someone be injured on school property after hours while participating in a recreational activity. Among those that did not allow community access, 91% were somewhat to very concerned about liability and 86% believed that stronger legislation was needed to better protect schools from liability for after-hours recreational use. Among those who claimed familiarity with a state law that offered them limited liability protection, nearly three fourths were nevertheless concerned about liability. Liability concerns are prevalent among this group of school administrators, particularly if they had been involved in prior litigation, and even if they indicated they were aware of laws that provide liability protection where use occurs after hours. Reducing these concerns will be important if schools are to become locations for recreational programs that promote physical activity outside of regular school hours. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

76 FR 58005 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... Aktiengesellschaft, Munich, Germany, a German corporation; Allianz of America, Inc., Novato, California, a Delaware corporation; Allianz Finanzbeteiligungs GMBH, Munich, Germany, a German limited liability company; and Allianz SE, Munich, Germany, a German corporation, to acquire voting shares of ECB Bancorp, Inc., and thereby...

26 CFR 1.752-3 - Partner's share of nonrecourse liabilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) INCOME TAX (CONTINUED) INCOME TAXES Provisions Common to Part II, Subchapter K, Chapter 1 of the Code § 1...) The partner's share of partnership minimum gain determined in accordance with the rules of section 704(b) and the regulations thereunder; (2) The amount of any taxable gain that would be allocated to the...

Friendship conflict and the development of generalized physical aggression in the early school years: a genetically informed study of potential moderators.

PubMed

Salvas, Marie-Claude; Vitaro, Frank; Brendgen, Mara; Dionne, Ginette; Tremblay, Richard E; Boivin, Michel

2014-06-01

Several authors consider high and frequent conflicts between friends during childhood as a serious risk for subsequent conduct problems such as generalized physical aggression toward others (e.g., Kupersmidt, Burchinal, & Patterson, 1995; Sebanc, 2003). Although it seems logical to assume that friendship conflict could have some negative consequences on children's behaviors, some scholars have suggested that a certain amount of conflict between friends may actually promote social adjustment (e.g., Laursen & Pursell, 2009). The aim of this study was to investigate the role of friendship conflict in regard to the development of generalized physical aggression toward others in the early school years (i.e., from kindergarten to Grade 1), as well as the moderating role of relational (i.e., shared positive affect and dyadic conflict resolution skills) and personal (i.e., children's sex and genetic liability for aggression) characteristics in this context. The sample included 745 twins assessed through teacher, peer, child, and friend ratings in kindergarten and Grade 1. Friendship conflict in kindergarten was linearly related to an increase in boys' but not girls' generalized physical aggression. However, shared positive affect and conflict resolution skills mitigated the prospective associations between friendship conflict and generalized physical aggression. These results were independent of children's sex, genetic risk for physical aggression, and initial levels of generalized physical aggression in kindergarten. Fostering a positive relationship between friends at school entry may buffer against the risk associated with experiencing friendship conflict. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Sources of individual differences in depressive symptoms: analysis of two samples of twins and their families.

PubMed

Kendler, K S; Walters, E E; Truett, K R; Heath, A C; Neale, M C; Martin, N G; Eaves, L J

1994-11-01

Self-reported symptoms of depression are commonly used in mental health research to assess current psychiatric state, yet wide variation in these symptoms among individuals has been found in both clinical and epidemiologic populations. The authors sought to understand, from a genetic-epidemiologic perspective, the sources of individual differences in depressive symptoms. Self-reported symptoms of depression were assessed in two samples of twins and their spouses, parents, siblings, and offspring: one sample contained volunteer twins recruited through the American Association of Retired Persons and their relatives (N = 19,203 individuals) and the other contained twins from a population-based twin registry in Virginia and their relatives (N = 11,242 individuals). Model fitting by an iterative, diagonal, weighted least squares method was applied to the 80 different family relationships in the extended twin-family design. Independent analyses of the two samples revealed that the level of depressive symptoms was modestly familial, and familial resemblance could be explained solely by genetic factors and spousal resemblance. The estimated heritability of depressive symptoms was between 30% and 37%. There was no evidence that the liability to depressive symptoms was environmentally transmitted from parents to offspring or was influenced by environmental factors shared either generally among siblings or specifically between twins. With correction for unreliability of measurement, genetic factors accounted for half of the stable variance in depressive symptoms. Depressive symptoms in adulthood partly reflect enduring characteristics of temperament that are substantially influenced by hereditary factors but little, or not at all, by shared environmental experiences in the family of origin.

ADHD and the externalizing spectrum: direct comparison of categorical, continuous, and hybrid models of liability in a nationally representative sample.

PubMed

Carragher, Natacha; Krueger, Robert F; Eaton, Nicholas R; Markon, Kristian E; Keyes, Katherine M; Blanco, Carlos; Saha, Tulshi D; Hasin, Deborah S

2014-08-01

Alcohol use disorders, substance use disorders, and antisocial personality disorder share a common externalizing liability, which may also include attention-deficit hyperactivity disorder (ADHD). However, few studies have compared formal quantitative models of externalizing liability, with the aim of delineating the categorical and/or continuous nature of this liability in the community. This study compares categorical, continuous, and hybrid models of externalizing liability. Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). Seven disorders were modeled: childhood ADHD and lifetime diagnoses of antisocial personality disorder (ASPD), nicotine dependence, alcohol dependence, marijuana dependence, cocaine dependence, and other substance dependence. The continuous latent trait model provided the best fit to the data. Measurement invariance analyses supported the fit of the model across genders, with females displaying a significantly lower probability of experiencing externalizing disorders. Cocaine dependence, marijuana dependence, other substance dependence, alcohol dependence, ASPD, nicotine dependence, and ADHD provided the greatest information, respectively, about the underlying externalizing continuum. Liability to externalizing disorders is continuous and dimensional in severity. The findings have important implications for the organizational structure of externalizing psychopathology in psychiatric nomenclatures.

7 CFR 1944.516 - Grant purposes.

Code of Federal Regulations, 2010 CFR

2010-01-01

... administrative costs such as workers' compensation, liability insurance, audit reports, travel to and attendance...'s share of Social Security and health benefits. Payments to private retirement funds are prohibited...

7 CFR 1944.516 - Grant purposes.

Code of Federal Regulations, 2011 CFR

2011-01-01

... administrative costs such as workers' compensation, liability insurance, audit reports, travel to and attendance...'s share of Social Security and health benefits. Payments to private retirement funds are prohibited...

Family Conflict Interacts with Genetic Liability in Predicting Childhood and Adolescent Depression

ERIC Educational Resources Information Center

Rice, Frances; Harold, Gordon T.; Shelton, Katherine H.; Thapar, Anita

2006-01-01

Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms…

Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits.

PubMed

Traglia, Michela; Bseiso, Dina; Gusev, Alexander; Adviento, Brigid; Park, Daniel S; Mefford, Joel A; Zaitlen, Noah; Weiss, Lauren A

2017-02-01

Common diseases often show sex differences in prevalence, onset, symptomology, treatment, or prognosis. Although studies have been performed to evaluate sex differences at specific SNP associations, this work aims to comprehensively survey a number of complex heritable diseases and anthropometric traits. Potential genetically encoded sex differences we investigated include differential genetic liability thresholds or distributions, gene-sex interaction at autosomal loci, major contribution of the X-chromosome, or gene-environment interactions reflected in genes responsive to androgens or estrogens. Finally, we tested the overlap between sex-differential association with anthropometric traits and disease risk. We utilized complementary approaches of assessing GWAS association enrichment and SNP-based heritability estimation to explore explicit sex differences, as well as enrichment in sex-implicated functional categories. We do not find consistent increased genetic load in the lower-prevalence sex, or a disproportionate role for the X-chromosome in disease risk, despite sex-heterogeneity on the X for several traits. We find that all anthropometric traits show less than complete correlation between the genetic contribution to males and females, and find a convincing example of autosome-wide genome-sex interaction in multiple sclerosis (P = 1 × 10 -9 ). We also find some evidence for hormone-responsive gene enrichment, and striking evidence of the contribution of sex-differential anthropometric associations to common disease risk, implying that general mechanisms of sexual dimorphism determining secondary sex characteristics have shared effects on disease risk. Copyright © 2017 by the Genetics Society of America.

12 CFR 559.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... stock, limited or general partnership interests, or shares in a limited liability company. Service... §§ 559.3(e)(2) and 559.4 of this part. Subordinate organization means any corporation, partnership...

Individual Differences in Exercise Behavior: Stability and Change in Genetic and Environmental Determinants From Age 7 to 18.

PubMed

Huppertz, Charlotte; Bartels, Meike; de Zeeuw, Eveline L; van Beijsterveldt, Catharina E M; Hudziak, James J; Willemsen, Gonneke; Boomsma, Dorret I; de Geus, Eco J C

2016-09-01

Exercise behavior during leisure time is a major source of health-promoting physical activity and moderately tracks across childhood and adolescence. This study aims to investigate the absolute and relative contribution of genes and the environment to variance in exercise behavior from age 7 to 18, and to elucidate the stability and change of genetic and shared environmental factors that underlie this behavior. The Netherlands Twin Register collected data on exercise behavior in twins aged approximately 7, 10, 12, 14, 16 and 18 years (N = 27,332 twins; 48 % males; 47 % with longitudinal assessments). Three exercise categories (low, middle, high) were analyzed by means of liability threshold models. First, a univariate model was fitted using the largest available cross-sectional dataset with linear and quadratic effects of age as modifiers on the means and variance components. Second, a simplex model was fitted on the longitudinal dataset. Heritability was low in 7-year-olds (14 % in males and 12 % in females), but gradually increased up to age 18 (79 % in males and 49 % in females), whereas the initially substantial relative influence of the shared environment decreased with age (from 80 to 4 % in males and from 80 to 19 % in females). This decrease was due to a large increase in the genetic variance. The longitudinal model showed the genetic effects in males to be largely stable and to accumulate from childhood to late adolescence, whereas in females, they were marked by both transmission and innovation at all ages. The shared environmental effects tended to be less stable in both males and females. In sum, the clear age-moderation of exercise behavior implies that family-based interventions might be useful to increase this behavior in children, whereas individual-based interventions might be better suited for adolescents. We showed that some determinants of individual differences in exercise behavior are stable across childhood and youth, whereas others come into play at specific ages. In view of the many benefits of regular exercise, identifying these determinants at specific ages should be a public health priority.

Short communication: Genetic association between schizophrenia and cannabis use.

PubMed

Verweij, Karin J H; Abdellaoui, Abdel; Nivard, Michel G; Sainz Cort, Alberto; Ligthart, Lannie; Draisma, Harmen H M; Minică, Camelia C; Gillespie, Nathan A; Willemsen, Gonneke; Hottenga, Jouke-Jan; Boomsma, Dorret I; Vink, Jacqueline M

2017-02-01

Previous studies have shown a relationship between schizophrenia and cannabis use. As both traits are substantially heritable, a shared genetic liability could explain the association. We use two recently developed genomics methods to investigate the genetic overlap between schizophrenia and cannabis use. Firstly, polygenic risk scores for schizophrenia were created based on summary statistics from the largest schizophrenia genome-wide association (GWA) meta-analysis to date. We analysed the association between these schizophrenia polygenic scores and multiple cannabis use phenotypes (lifetime use, regular use, age at initiation, and quantity and frequency of use) in a sample of 6,931 individuals. Secondly, we applied LD-score regression to the GWA summary statistics of schizophrenia and lifetime cannabis use to calculate the genome-wide genetic correlation. Polygenic risk scores for schizophrenia were significantly (α<0.05) associated with five of the eight cannabis use phenotypes, including lifetime use, regular use, and quantity of use, with risk scores explaining up to 0.5% of the variance. Associations were not significant for age at initiation of use and two measures of frequency of use analyzed in lifetime users only, potentially because of reduced power due to a smaller sample size. The LD-score regression revealed a significant genetic correlation of r g =0.22 (SE=0.07, p=0.003) between schizophrenia and lifetime cannabis use. Common genetic variants underlying schizophrenia and lifetime cannabis use are partly overlapping. Individuals with a stronger genetic predisposition to schizophrenia are more likely to initiate cannabis use, use cannabis more regularly, and consume more cannabis over their lifetime. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heritability of Tic Disorders: a Twin-Family Study

PubMed Central

Zilhao, Nuno R.; Olthof, Maria C.; Smit, Dirk J.A.; Cath, Danielle C.; Ligthart, Lannie; Mathews, Carol A.; Delucchi, Kevin; Boomsma, Dorret I.; Dolan, Conor V.

2017-01-01

Background Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. Methods In an extended twin-family design, we analyzed lifetime tic data reported by adult mono- and dizygotic twins (n= 8,323) and their family members (n=7,164; parents and siblings) from 7,311 families in the Netherlands Twin Register (NTR). We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes (STOBS) (TSAICG, 2007). Heritability was estimated by genetic Structural Equation Modeling (SEM) for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. Results Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between .25 and .37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment, or non-additive genetic effects. Conclusions Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSMIV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies. PMID:27974054

The Role of Genetics in IBS

PubMed Central

Saito, Yuri A.

2011-01-01

IBS is a common disorder that has been shown to aggregate in families, to affect multiple generations, but not in a manner consistent with a major Mendelian effect. Relatives of an individual with IBS are two to three times as likely to have IBS, with both genders being affected. The estimated genetic liability ranges between 1–20%, with heritability estimates ranging between 0–57%. Although the role of childhood events such as nasogastric tube placement, poor nutrition, abuse, and other stressors have been clearly associated with IBS, these factors have not been studied in families and are unlikely to completely explain the clustering of bowel dysfunction observed in family studies. Furthermore, the familial clustering of IBS does not appear to be explained by psychological traits, based on family studies as well as candidate gene studies of functional variants associated with other psychiatric disorders. To date, over a hundred genetic variants in over 60 genes from various pathways have been studied in a number of candidate gene studies with several positive associations reported. These findings suggest that there may be distinct, as well as shared, molecular underpinnings for IBS and its subtypes. Much new and confirmatory work remains to be performed to elucidate the role of specific genetic variants in IBS development, as well as the specific ways the genes and environment interact to result in IBS susceptibility. PMID:21333900

A twin study of specific bulimia nervosa symptoms.

PubMed

Mazzeo, S E; Mitchell, K S; Bulik, C M; Aggen, S H; Kendler, K S; Neale, M C

2010-07-01

Twin studies have suggested that additive genetic factors significantly contribute to liability to bulimia nervosa (BN). However, the diagnostic criteria for BN remain controversial. In this study, an item-factor model was used to examine the BN diagnostic criteria and the genetic and environmental contributions to BN in a population-based twin sample. The validity of the equal environment assumption (EEA) for BN was also tested. Participants were 1024 female twins (MZ n=614, DZ n=410) from the population-based Mid-Atlantic Twin Registry. BN was assessed using symptom-level (self-report) items consistent with DSM-IV and ICD-10 diagnostic criteria. Items assessing BN were included in an item-factor model. The EEA was measured by items assessing similarity of childhood and adolescent environment, which have demonstrated construct validity. Scores on the EEA factor were used to specify the degree to which twins shared environmental experiences in this model. The EEA was not violated for BN. Modeling results indicated that the majority of the variance in BN was due to additive genetic factors. There was substantial variability in additive genetic and environmental contributions to specific BN symptoms. Most notably, vomiting was very strongly influenced by additive genetic factors, while other symptoms were much less heritable, including the influence of weight on self-evaluation. These results highlight the importance of assessing eating disorders at the symptom level. Refinement of eating disorder phenotypes could ultimately lead to improvements in treatment and targeted prevention, by clarifying sources of variation for specific components of symptomatology.

Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits

PubMed Central

Traglia, Michela; Bseiso, Dina; Gusev, Alexander; Adviento, Brigid; Park, Daniel S.; Mefford, Joel A.; Zaitlen, Noah; Weiss, Lauren A.

2017-01-01

Common diseases often show sex differences in prevalence, onset, symptomology, treatment, or prognosis. Although studies have been performed to evaluate sex differences at specific SNP associations, this work aims to comprehensively survey a number of complex heritable diseases and anthropometric traits. Potential genetically encoded sex differences we investigated include differential genetic liability thresholds or distributions, gene–sex interaction at autosomal loci, major contribution of the X-chromosome, or gene–environment interactions reflected in genes responsive to androgens or estrogens. Finally, we tested the overlap between sex-differential association with anthropometric traits and disease risk. We utilized complementary approaches of assessing GWAS association enrichment and SNP-based heritability estimation to explore explicit sex differences, as well as enrichment in sex-implicated functional categories. We do not find consistent increased genetic load in the lower-prevalence sex, or a disproportionate role for the X-chromosome in disease risk, despite sex-heterogeneity on the X for several traits. We find that all anthropometric traits show less than complete correlation between the genetic contribution to males and females, and find a convincing example of autosome-wide genome-sex interaction in multiple sclerosis (P = 1 × 10−9). We also find some evidence for hormone-responsive gene enrichment, and striking evidence of the contribution of sex-differential anthropometric associations to common disease risk, implying that general mechanisms of sexual dimorphism determining secondary sex characteristics have shared effects on disease risk. PMID:27974502

Common variants explain a large fraction of the variability in the liability to psoriasis in a Han Chinese population.

PubMed

Yin, Xianyong; Wineinger, Nathan E; Cheng, Hui; Cui, Yong; Zhou, Fusheng; Zuo, Xianbo; Zheng, Xiaodong; Yang, Sen; Schork, Nicholas J; Zhang, Xuejun

2014-01-30

Psoriasis is a common inflammatory skin disease with a known genetic component. Our previously published psoriasis genome-wide association study identified dozens of novel susceptibility loci in Han Chinese. However, these markers explained only a small fraction of the estimated heritable component of psoriasis. To better understand the unknown yet likely polygenic architecture in psoriasis, we applied a linear mixed model to quantify the variation in the liability to psoriasis explained by common genetic markers (minor allele frequency > 0.01) in a Han Chinese population. We explored the polygenic genetic architecture of psoriasis using genome-wide association data from 2,271 Han Chinese individuals. We estimated that 34.9% (s.e. = 6.0%, P = 9 × 10-9) of the variation in the liability to psoriasis is captured by common genotyped and imputed variants. We discuss these results in the context of the strong association between HLA variants and psoriasis. We also show that the variance explained by each chromosome is linearly correlated to its length (R2 = 0.27, P=0.01), and quantify the impact of a polygenic effect on the prediction and diagnosis of psoriasis. Our results suggest that psoriasis has a substantial polygenic component, which not only has implications for the development of genetic diagnostics and prognostics for psoriasis, but also suggests that more individual variants contributing to psoriasis may be detected if sample sizes in future association studies are increased.

Model Invariance across Genders of the Broad Autism Phenotype Questionnaire

ERIC Educational Resources Information Center

Broderick, Neill; Wade, Jordan L.; Meyer, J. Patrick; Hull, Michael; Reeve, Ronald E.

2015-01-01

ASD is one of the most heritable neuropsychiatric disorders, though comprehensive genetic liability remains elusive. To facilitate genetic research, researchers employ the concept of the broad autism phenotype (BAP), a milder presentation of traits in undiagnosed relatives. Research suggests that the BAP Questionnaire (BAPQ) demonstrates…

Genetic Risks and ADHD Symptomatology: Exploring the Effects of Parental Antisocial Behaviors in an Adoption-Based Study

ERIC Educational Resources Information Center

Beaver, Kevin M.; Nedelec, Joseph L.; Rowland, Meghan W.; Schwartz, Joseph A.

2012-01-01

A great deal of research has examined the etiology of attention-deficit/hyperactivity disorder (ADHD) and ADHD symptomatologies. Genetic factors are consistently shown to explain a significant proportion of variance in measures of ADHD. The current study adds to this body of research by examining whether genetic liabilities for criminality and…

A twin study of early-childhood asthma in Puerto Ricans.

PubMed

Bunyavanich, Supinda; Silberg, Judy L; Lasky-Su, Jessica; Gillespie, Nathan A; Lange, Nancy E; Canino, Glorisa; Celedón, Juan C

2013-01-01

The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood. To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤ 3 years old. 678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages 1 and 3 years: physician-diagnosed asthma, asthma medication use in the past year, and ≥ 1 hospitalization for asthma in the past year. Models were additionally adjusted for early-life environmental tobacco smoke exposure, sex, and age. The prevalences of physician-diagnosed asthma, asthma medication use, and hospitalization for asthma were 11.6%, 10.8%, 4.9% at age 1 year, and 34.1%, 40.1%, and 8.5% at 3 years, respectively. Shared environmental effects contributed to the majority of variance in susceptibility to physician-diagnosed asthma and asthma medication use in the first year of life (84%-86%), while genetic effects drove variance in all phenotypes (45%-65%) at age 3 years. Early-life environmental tobacco smoke, sex, and age contributed to variance in susceptibility. Our longitudinal study in Puerto Rican twins demonstrates a changing contribution of shared environmental effects to liability for physician-diagnosed asthma and asthma medication use between ages 1 and 3 years. Early-life environmental tobacco smoke reduction could markedly reduce asthma morbidity in young Puerto Rican children.

Disordered gambling as defined by the Diagnostic and Statistical Manual of Mental Disorders and the South Oaks Gambling Screen: evidence for a common etiologic structure.

PubMed

Slutske, Wendy S; Zhu, Gu; Meier, Madeline H; Martin, Nicholas G

2011-08-01

In a previous article, we demonstrated in a large twin study that disordered gambling (DG), as defined by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV), ran in families, that about half of the variation in liability for DG was due to familial factors, and that all of this was explained by shared genetic rather than shared environmental influences (Slutske, Zhu, Meier, & Martin, 2010). The purpose of the present study is to extend this work to include an alternative conceptualization of DG that is provided by the South Oaks Gambling Screen (SOGS) item set in order to (a) compare the magnitude of the familial resemblance obtained when using the two definitions of DG (based on the DSM-IV and the SOGS), (b) examine the extent to which the 2 definitions tap the same underlying sources of genetic and environmental variation, and (c) examine whether the same results will be obtained among men and women. The results of bivariate twin model-fitting analyses suggested that DG, as defined by the DSM-IV and the SOGS, substantially overlapped at the etiologic level among both men and women, which supports the construct validity of both the DSM and the SOGS conceptualizations of DG. This study highlights the utility of twin studies for appraising the validity of the diagnostic nomenclature. © 2011 American Psychological Association

Genetic and environmental influences on the comorbidity between depression, panic disorder, agoraphobia and social phobia: A twin study

PubMed Central

Mosing, Miriam A.; Gordon, Scott D.; Medland, Sarah E.; Statham, Dixie J.; Nelson, Elliot C.; Heath, Andrew C.; Martin, Nicholas G.; Wray, Naomi R.

2011-01-01

Background Major depression (MD) and anxiety disorders such as panic disorder (PD), agoraphobia (AG) and social phobia (SP) are heritable and highly comorbid. However, the relative importance of genetic and environmental aetiology of the covariation between these disorders, particularly the relationship between PD and AG is less clear. Methods The present study measured MD, PD and AG in a population sample of 5440 twin pairs and 1245 single twins, about 45% of whom were also scored for SP. Prevalences, within individual comorbidity and twin odds ratios for comorbidity are reported. A behavioural genetic analysis of the four disorders using the classical twin design was conducted. Results Odds ratios for MD, PD, AG, and SP in twins of individuals diagnosed with one of the four disorders were increased. Heritability estimates under a threshold-liability model for MD, PD, AG, and SP respectively were 0.33 (CI:0.30–0.42), 0.38 (CI:0.24–0.55), 0.48 (CI:0.37–0.65) of, and 0.39 (CI:0.16–0.65), with no evidence for any variance explained by the common environment shared by twins. We find that a common genetic factor explains a moderate proportion of variance in these four disorders. The genetic correlation between PD and AG was 0.83. Conclusion MD, PD, AG, and SP strongly co-aggregate within families and common genetic factors explain a moderate proportion of variance in these four disorders. The high genetic correlation between PD and AG and the increased odds ratio for PD and AG in siblings of those with AG without PD suggests a common genetic aetiology for PD and AG. PMID:19750555

Genetic and environmental influences on the co-morbidity between depression, panic disorder, agoraphobia, and social phobia: a twin study.

PubMed

Mosing, Miriam A; Gordon, Scott D; Medland, Sarah E; Statham, Dixie J; Nelson, Elliot C; Heath, Andrew C; Martin, Nicholas G; Wray, Naomi R

2009-01-01

Major depression (MD) and anxiety disorders such as panic disorder (PD), agoraphobia (AG), and social phobia (SP) are heritable and highly co-morbid. However, the relative importance of genetic and environmental etiology of the covariation between these disorders, particularly the relationship between PD and AG, is less clear. This study measured MD, PD, and AG in a population sample of 5,440 twin pairs and 1,245 single twins, about 45% of whom were also scored for SP. Prevalences, within individual co-morbidity and twin odds ratios for co-morbidity, are reported. A behavioral genetic analysis of the four disorders using the classical twin design was conducted. Odds ratios for MD, PD, AG, and SP in twins of individuals diagnosed with one of the four disorders were increased. Heritability estimates under a threshold-liability model for MD, PD, AG, and SP respectively were .33 (CI: 0.30-0.42), .38 (CI: 0.24-0.55), .48 (CI: 0.37-0.65), and .39 (CI: 0.16-0.65), with no evidence for any variance explained by the common environment shared by twins. We find that a common genetic factor explains a moderate proportion of variance in these four disorders. The genetic correlation between PD and AG was .83. MD, PD, AG, and SP strongly co-aggregate within families and common genetic factors explain a moderate proportion of variance in these four disorders. The high genetic correlation between PD and AG and the increased odds ratio for PD and AG in siblings of those with AG without PD suggests a common genetic etiology for PD and AG.

7 CFR 785.4 - Grants to certified State mediation programs.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., liability insurance, employer's share of Social Security, and travel that is necessary to provide mediation.... Expenditures of grant funds are not allowed for: (i) Purchase of capital assets, real estate, or vehicles and...

7 CFR 785.4 - Grants to certified State mediation programs.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., liability insurance, employer's share of Social Security, and travel that is necessary to provide mediation.... Expenditures of grant funds are not allowed for: (i) Purchase of capital assets, real estate, or vehicles and...

Social-Cognition and the Broad Autism Phenotype: Identifying Genetically Meaningful Phenotypes

ERIC Educational Resources Information Center

Losh, Molly; Piven, Joseph

2007-01-01

Background: Strong evidence from twin and family studies suggests that the genetic liability to autism may be expressed through personality and language characteristics qualitatively similar, but more subtly expressed than those defining the full syndrome. This study examined behavioral features of this "broad autism phenotype" (BAP) in relation…

Analysis of Behavioral and Emotional Problems in Children Highlights the Role of Genotype × Environment Interaction.

PubMed

Molenaar, Dylan; Middeldorp, Christel; van Beijsterveldt, Toos; Boomsma, Dorret I

2015-01-01

This study tested for Genotype × Environment (G × E) interaction on behavioral and emotional problems in children using new methods that do not require identification of candidate genes or environments, can distinguish between interaction with shared and unique environment, and are insensitive to scale effects. Parental ratings of problem behavior from 14,755 twin pairs (5.3 years, SD = 0.22) indicated G × E interaction on emotional liability, social isolation, aggression, attention problems, dependency, anxiety, and physical coordination. Environmental influences increased in children who were genetically more predisposed to problem behavior, with ~20% of the variance due to G × E interaction (8% for anxiety to 37% for attention problems). Ignoring G × E interaction does not greatly bias heritability estimates, but it does offer a comprehensive model of the etiology for childhood problems. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

Development of liability syndromes for schizophrenia: where did they come from and where are they going?

PubMed

Stone, William S; Giuliano, Anthony J

2013-10-01

Three decades after Paul Meehl proposed the term "schizotaxia" to describe a conceptual framework for understanding the liability to schizophrenia, Ming Tsuang et al. at Harvard University reformulated the concept as a clinical syndrome with provisional research criteria. The reformulated view relied heavily on more recent data showing that many non-psychotic, un-medicated biological relatives of individuals with schizophrenia showed difficulties in cognitive and other clinical functions that resembled those seen in their ill relatives. The reformulation raised questions about both whether and when liability could be assessed validly in the absence of psychosis, and about the extent to which symptoms of liability are reversible. Both questions bear on the larger issue of early intervention in schizophrenia. This article reviews the efforts of Tsuang et al. to conceptualize and validate schizotaxia as one such syndrome of liability. Towards this end, liability is considered first more generally as an outcome of interactive genetic and environmental factors. Liability is then considered in the context of endophenotypes as a concept that is both broader and is potentially more specific (and predictive) than many DSM or ICD diagnostic symptoms. Liability syndromes are then considered in the context of their proximity to illness, first by reviewing prodromal syndromes (which are more proximal), and then by considering schizotaxia, which, as it is currently formulated, is pre-prodromal and, therefore, less proximal. Finally, challenges to validation and future directions for research are considered. © 2013 Wiley Periodicals, Inc.

Beyond Sister City Agreements: Exploring the Challenges of Full International Interoperability

DTIC Science & Technology

2016-03-01

are often interconnected by more than simple proximity. They are connected through social networks, economy, culture, and shared natural resources...southern U.S. borders to determine how various regions address their cross-border agreements. Research indicated that unique challenges—such as liability...They are connected through social networks, economy, culture, and shared natural resources. Despite this interdependent relationship, and in spite

Schizophrenia and the androgen receptor gene: Report of a sibship showing co-segregation with Reifenstein Syndrome but no evidence for linkage in 23 multiply affected families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arranz, M.; Sharma, T.; Sham, P.

Crow et al. have reported excess sharing of alleles by male sibling pairs with schizophrenia, at a triplet repeat marker within the androgen receptor gene, indicating that mutations at or near this gene may be a risk factor for males. In this report, we describe a pair of male siblings concordant for both schizophrenia and Reifenstein syndrome, which is caused by a mutation in this gene. This provides support for the hypothesis that the androgen receptor may contribute to liability to develop schizophrenia. Because of this, we have examined a collection of 23 pedigrees multiply affected by schizophrenia for linkagemore » to the androgen receptor. We have found no evidence for linkage by both the LOD score and affected sibling-pair methods, under a range of genetic models with a broad and narrow definition of phenotype, and when families with male-to-male transmission are excluded. However, because of the small number of informative male-male pairs in our sample, we cannot confirm or refute the excess allele sharing for males reported by Crow. 35 refs., 1 fig., 2 tabs.« less

Gambling, disordered gambling and their association with major depression and substance use: a web-based cohort and twin-sibling study.

PubMed

Blanco, C; Myers, J; Kendler, K S

2012-03-01

Relatively little is known about the environmental and genetic contributions to gambling frequency and disordered gambling (DG), the full continuum of gambling-related problems that includes pathological gambling (PG). A web-based sample (n=43,799 including both members of 609 twin and 303 sibling pairs) completed assessments of number of lifetime gambling episodes, DSM-IV criteria for PG, alcohol, nicotine and caffeine intake, and nicotine dependence (ND) and DSM-III-R criteria for lifetime major depression (MD). Twin modeling was performed using Mx. In the entire cohort, symptoms of DG indexed a single dimension of liability. Symptoms of DG were weakly related to caffeine intake and moderately related to MD, consumption of cigarettes and alcohol, and ND. In twin and sibling pairs, familial resemblance for number of times gambled resulted from both familial-environmental (c²=42%) and genetic factors (a²=32%). For symptoms of DG, resemblance resulted solely from genetic factors (a²=83%). Bivariate analyses indicated a low genetic correlation between symptoms of DG and MD (r(a)=+0.14) whereas genetic correlations with DG symptoms were substantially higher with use of alcohol, caffeine and nicotine, and ND (ranging from +0.29 to +0.80). The results were invariant across genders. Whereas gambling participation is determined by shared environmental and genetic factors, DG constitutes a single latent dimension that is largely genetically determined and more closely related to externalizing than internalizing behaviors. Because these findings are invariant across genders, they suggest that the etiological factors of DG are likely to be similar in men and women.

Liability risk sharing regime for U.S. commercial space transportation : study and analysis

DOT National Transportation Integrated Search

2002-04-01

The Federal Aviation Administration of the Department of Transportation (DOT), in cooperation with interested federal agencies, has performed a study and analysis of seven issues specifically identified in the Space Competitiveness Act, and provides ...

Document Delivery: An Annotated Selective Bibliography.

ERIC Educational Resources Information Center

Khalil, Mounir A.; Katz, Suzanne R.

1992-01-01

Presents a selective annotated bibliography of 61 items that deal with topics related to document delivery, including networks; hypertext; interlibrary loan; computer security; electronic publishing; copyright; online catalogs; resource sharing; electronic mail; electronic libraries; optical character recognition; microcomputers; liability issues;…

Genetic etiology in cases of recovered and persistent stuttering in an unselected, longitudinal sample of young twins.

PubMed

Dworzynski, Katharina; Remington, Anna; Rijsdijk, Frühling; Howell, Peter; Plomin, Robert

2007-05-01

The contribution of genetic factors in the persistence of and early recovery from stuttering was assessed. Data from the Twins Early Development Study were employed. Parental reports regarding stuttering were collected at ages 2, 3, 4, and 7 years, and were used to classify speakers into recovered and persistent groups. Of 12,892 children with at least 2 ratings, 950 children had recovered and 135 persisted in their stutter. Logistic regressions showed that the rating at age 2 was not predictive of later stuttering, whereas ratings at ages 3 and 4 were. Concordance rates were consistently higher for monozygotic than for dizygotic twin pairs (with the exception of girls at age 3). At 3, 4, and 7 years, the liability to stuttering was highly heritable (h2 estimates of between .58 and .66). Heritability for the recovered and persistent groups was also high but did not differ from each other. Stuttering appears to be a disorder that has high heritability and little shared environment effect in early childhood and for recovered and persistent groups of children, by age 7. The clinical implications of the findings are discussed.

Genetic etiology in cases of recovered and persistent stuttering in an unselected, longitudinal sample of young twins

PubMed Central

Dworzynski, Katharina; Remington, Anna; Rijsdijk, Frühling; Howell, Peter; Plomin, Robert

2007-01-01

Purpose The contribution of genetic factors in persistence and early recovery from stuttering was assessed.. Method Data from the Twins Early Development Study were employed. Parental reports regarding stuttering were collected at ages 2, 3, 4 and 7 years and were used to classify speakers into recovered and persistent groups. Of 12,892 children with at least two ratings, 950 children had recovered and 135 persisted in their stutter. Results Logistic regressions showed that the rating at age 2 was not predictive of later stuttering, whereas ratings at ages 3 and 4 were. Concordance rates were consistently higher for monozygotic than for dizygotic twin pairs (with the exception of girls at age 3). At 3, 4 and 7 years, the liability to stuttering was highly heritable (h2 estimates of between .58 and .66). Heritability for the recovered and persistent groups was also high, but did not differ from each other. Conclusion Stuttering appears to be a disorder that has high heritability and little shared environment effect in early childhood and for recovered and persistent groups of children, by age 7. The clinical implications of the findings are discussed. PMID:17456895

Spatial working memory function in twins with schizophrenia and bipolar disorder.

PubMed

Pirkola, Tiia; Tuulio-Henriksson, Annamari; Glahn, David; Kieseppä, Tuula; Haukka, Jari; Kaprio, Jaakko; Lönnqvist, Jouko; Cannon, Tyrone D

2005-12-15

Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proband among the unaffected co-twins of schizophrenic patients. Here, we evaluated whether such deficits might also mark genetic susceptibility to bipolar disorder. The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures. Our findings support the hypothesis that impairment in spatial working memory might effectively reflect an expression of genetic liability to schizophrenia but less clearly to bipolar disorder.

Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease

PubMed Central

Do, Chuong B.; Tung, Joyce Y.; Dorfman, Elizabeth; Kiefer, Amy K.; Drabant, Emily M.; Francke, Uta; Mountain, Joanna L.; Goldman, Samuel M.; Tanner, Caroline M.; Langston, J. William; Wojcicki, Anne; Eriksson, Nicholas

2011-01-01

Although the causes of Parkinson's disease (PD) are thought to be primarily environmental, recent studies suggest that a number of genes influence susceptibility. Using targeted case recruitment and online survey instruments, we conducted the largest case-control genome-wide association study (GWAS) of PD based on a single collection of individuals to date (3,426 cases and 29,624 controls). We discovered two novel, genome-wide significant associations with PD–rs6812193 near SCARB2 (, ) and rs11868035 near SREBF1/RAI1 (, )—both replicated in an independent cohort. We also replicated 20 previously discovered genetic associations (including LRRK2, GBA, SNCA, MAPT, GAK, and the HLA region), providing support for our novel study design. Relying on a recently proposed method based on genome-wide sharing estimates between distantly related individuals, we estimated the heritability of PD to be at least 0.27. Finally, using sparse regression techniques, we constructed predictive models that account for 6%–7% of the total variance in liability and that suggest the presence of true associations just beyond genome-wide significance, as confirmed through both internal and external cross-validation. These results indicate a substantial, but by no means total, contribution of genetics underlying susceptibility to both early-onset and late-onset PD, suggesting that, despite the novel associations discovered here and elsewhere, the majority of the genetic component for Parkinson's disease remains to be discovered. PMID:21738487

Risk Factors Influencing Smoking Behavior: A Turkish Twin Study

PubMed Central

Öncel, Sevgi Yurt; Dick, Danielle M.; Maes, Hermine H.; Alıev, Fazil

2015-01-01

Aim In this study, we introduce the first twin study in Turkey, focusing on smoking behavior, and laying the foundation to register all twins born in Turkey for research purposes. Using Turkish twins will contribute to our understanding of health problems in the context of cultural differences. Materials and methods We assessed 309 twin pairs (339 males and 279 females) aged between 15 and 45 years living in the Kırıkkale and Ankara regions of Turkey, and administered a health and lifestyle interview that included questions about smoking status and smoking history. We analyzed the data using descriptive statistics, t-tests, chi-square tests, and bivariate and multivariate clustered logistic regression. In addition, we fit bivariate Structural Equation Models (SEM) to determine contributions of latent genetic and environmental factors to smoking outcomes in this sample. Results One hundred seventy-eight participants (28.8%) were identified as smokers, smoking every day for a month or longer, of whom 79.2% were males and 20.8% were females. Mean values for number of cigarettes per day and the Fagerstrom Test of Nicotine Dependence (FTND; Fagerstrom, 1978) score were higher in males than in females, and age of onset was earlier in males. There was a significant positive correlation between the FTND score and number of cigarettes smoked per day, and a significant negative correlation between both variables and age at onset of smoking. Our study showed that gender, presence of a smoking twin in the family, age, alcohol use, marital status, daily sports activities, and feeling moody all played a significant role in smoking behavior among twins. The twin analysis suggested that 79.5% of the liability to FTND was influenced by genetic factors and 20.5% by unique environment, while familial resemblance for smoking initiation was best explained by common environmental factors. Conclusions Marked differences in the prevalence of smoking behavior in men versus women were observed for the Turkish population. Genetic analyses showed that common environmental factors primarily contributed to smoking initiation, while genetic factors explained a greater proportion of variance in liability to nicotine dependence. Our study shows higher heritability estimate of the FTND scores and higher shared environmental influence on smoking initiation for both males and females than reported in previous studies. PMID:25431287

Most genetic risk for autism resides with common variation

PubMed Central

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J.; Bodea, Corneliu A.; Goldberg, Arthur P.; Lee, Ann B.; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M.; Devlin, Bernie

2014-01-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (henceforth autism) the nature of its allelic spectrum is uncertain. Individual risk genes have been identified from rare variation, especially de novo mutations1–8. From this evidence one might conclude that rare variation dominates its allelic spectrum, yet recent studies show that common variation, individually of small effect, has substantial impact en masse9,10. At issue is how much of an impact relative to rare variation. Using a unique epidemiological sample from Sweden, novel methods that distinguish total narrow-sense heritability from that due to common variation, and by synthesizing results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is ≈54% and most traces to common variation; rare de novo mutations contribute substantially to individuals’ liability; still their contribution to variance in liability, 2.6%, is modest compared to heritable variation. PMID:25038753

Most genetic risk for autism resides with common variation.

PubMed

Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J; Bodea, Corneliu A; Goldberg, Arthur P; Lee, Ann B; Mahajan, Milind; Manaa, Dina; Pawitan, Yudi; Reichert, Jennifer; Ripke, Stephan; Sandin, Sven; Sklar, Pamela; Svantesson, Oscar; Reichenberg, Abraham; Hultman, Christina M; Devlin, Bernie; Roeder, Kathryn; Buxbaum, Joseph D

2014-08-01

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism's genetic architecture: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.

Integrating social science and behavioral genetics: testing the origin of socioeconomic disparities in depression using a genetically informed design.

PubMed

Mezuk, Briana; Myers, John M; Kendler, Kenneth S

2013-10-01

We tested 3 hypotheses-social causation, social drift, and common cause-regarding the origin of socioeconomic disparities in major depression and determined whether the relationship between socioeconomic status (SES) and major depression varied by genetic liability for major depression. Data were from a sample of female twins in the baseline Virginia Adult Twin Study of Psychiatric and Substance Use Disorders interviewed between 1987 and 1989 (n = 2153). We used logistic regression and structural equation twin models to evaluate these 3 hypotheses. Consistent with the social causation hypothesis, education (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.66, 0.93; P < .01) and income (OR = 0.93; 95% CI = 0.89, 0.98; P < .01) were significantly related to past-year major depression. Upward social mobility was associated with lower risk of depression. There was no evidence that childhood SES was related to development of major depression (OR = 0.98; 95% CI = 0.89, 1.09; P > .1). Consistent with a common genetic cause, there was a negative correlation between the genetic components of major depression and education (r(2) = -0.22). Co-twin control analyses indicated a protective effect of education and income on major depression even after accounting for genetic liability. This study utilized a genetically informed design to address how social position relates to major depression. Results generally supported the social causation model.

Familial liability for metoprolol-induced psychosis.

PubMed

Rietveld, L; van der Hoek, T; van Beek, M H C T; Schellekens, A F A

2015-01-01

Beta-blockers are commonly used in the treatment of hypertension and cardiac arrhythmias. The incidence of neuropsychiatric side effects is generally low. This case report shows the potential familial liability of a metoprolol-induced psychosis. We report a case of metoprolol-induced psychosis. Potential pharmocogenetic factors mediating this familial metoprolol-induced psychosis are discussed. A middle-aged man developed psychosis after starting metoprolol, which diminished after ceasing the medication. Two of his family members experienced similar symptoms after using metoprolol. All family members were genotyped as CYP2D6*4 allele carriers indicating reduced CYP2D6 enzyme activity. The case presented here suggests a potential familial liability for metoprolol- induced psychosis. Pharmacokinetic mechanisms are hypothesized to mediate this familial liability through genetic variation in the CYP2D6 genotype. A family history of psychotic symptoms after treatment with beta-blockers should be taken into account, when prescribing this beta-blocker. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic and Environmental Effects on Stuttering: A Twin Study from Finland

ERIC Educational Resources Information Center

Rautakoski, Pirkko; Hannus, Therese; Simberg, Susanna; Sandnabba, N. Kenneth; Santtila, Pekka

2012-01-01

The present study explored the prevalence of self-reported stuttering in a Finnish twin population and examined the extent to which the variance in liability to stuttering was attributable to genetic and environmental effects. We analyzed data of 1728 Finnish twins, born between 1961 and 1989. The participants were asked to complete a…

Kindergarten Children's Genetic Vulnerabilities Interact with Friends' Aggression to Promote Children's Own Aggression

ERIC Educational Resources Information Center

van Lier, Pol; Boivin, Michel; Dionne, Ginette; Vitaro, Frank; Brendgen, Mara; Koot, Hans; Tremblay, Richard E.; Perusse, Daniel

2007-01-01

Objective: To examine whether kindergarten children's genetic liability to physically aggress moderates the contribution of friends' aggression to their aggressive behaviors. Method: Teacher and peer reports of aggression were available for 359 6-year-old twin pairs (145 MZ, 212 DZ) as well as teacher and peer reports of aggression of the two best…

Sharing the Knowledge: Government-Private Sector Partnerships to Enhance Information Security

DTIC Science & Technology

2000-05-01

private sector . However, substantial barriers threaten to block information exchanges between the government and private sector . These barriers include concerns over release of sensitive material under Freedom of Information Act requests, antitrust actions, protection of business confidential and other private material, possible liability due to shared information, disclosure of classified information, and burdens entailed with cooperating with law enforcement agencies. There is good cause to believe that the government and private

Shared liability? Consultants, pharmacists, and the emergency physician: legal cases and caveats.

PubMed

Moore, Joshua J; Matlock, Aaron G

2014-05-01

In caring for patients in the Emergency Department (ED), the emergency physician (EP) will often utilize consulting specialists and pharmacists. In the event of an untoward patient outcome, disagreement may arise regarding the liability of each provider. Here, we review a series of malpractice cases involving consulting physicians and pharmacists to illustrate the legal principles of physician-patient relationships and physician duty. Determination of liability in the courts will rest, in part, on whether a physician-patient relationship was formed via an "affirmative act". Consulting physicians may establish a relationship through an overt or implied agreement to participate in a patient's care, or by reviewing specific tests and studies for the purpose of diagnosis and treatment. The courts have defined the duty of the pharmacist to safely dispense medication, and have ascribed the duty to warn of medication side effects to the prescribing physician. Published by Elsevier Inc.

When Your Dorms Become Their Business.

ERIC Educational Resources Information Center

Biddison, Gail B.; Hier, Thomas C.

1996-01-01

As more colleges and universities consider privatization of college housing, without many existing models to observe, institutions are encouraged to consider these issues before making a decision: in loco parentis responsibility; legal liability; shared obligations; financial arrangements and performance criteria; vendor responsibility for capital…

Effects of child maltreatment and inherited liability on antisocial development: an official records study.

PubMed

Jonson-Reid, Melissa; Presnall, Ned; Drake, Brett; Fox, Louis; Bierut, Laura; Reich, Wendy; Kane, Phyllis; Todd, Richard D; Constantino, John N

2010-04-01

Evidence is steadily accumulating that a preventable environmental hazard, child maltreatment, exerts causal influences on the development of long-standing patterns of antisocial behavior in humans. The relationship between child maltreatment and antisocial outcome, however, has never previously been tested in a large-scale study in which official reports (rather than family member reports) of child abuse and neglect were incorporated, and genetic influences comprehensively controlled for. We cross-referenced official report data on child maltreatment from the Missouri Division of Social Services (DSS) with behavioral data from 4,432 epidemiologically ascertained Missouri twins from the Missouri Twin Registry (MOTWIN). We performed a similar procedure for a clinically ascertained sample of singleton children ascertained from families affected by alcohol dependence participating in the Collaborative Study on the Genetics of Alcoholism (COGA; n = 428) to determine whether associations observed in the general population held true in an "enriched" sample at combined inherited and environmental risk for antisocial development. For both the twin and clinical samples, the additive effects (not interactive effects) of maltreatment and inherited liability on antisocial development were confirmed and were highly statistically significant. Child maltreatment exhibited causal influence on antisocial outcome when controlling for inherited liability in both the general population and in a clinically ascertained sample. Official report maltreatment data represents a critical resource for resolving competing hypotheses on genetic and environmental causation of child psychopathology, and for assessing intervention outcomes in efforts to prevent antisocial development.

Hereditary neuropathy with liability to pressure palsy: two cases of difficult diagnosis.

PubMed

Beydoun, Said R; Cho, Justin

2013-09-01

Hereditary neuropathy with liability to pressure palsies (HNPP) is an inherited autosomal dominant disorder that causes a polyneuropathy with predisposition for involvement at sites of compression and is often underdiagnosed or misdiagnosed due to its heterogeneity in clinical and electrophysiological presentation. We report 2 cases of HNPP, which were initially diagnosed and treated as either an acquired demyelinating disorder or alternative inherited demyelinating disorder. Thorough evaluation of repeat electrodiagnostic studies and genetic testing confirmed the diagnosis of HNPP in both cases. One case showed the classic peripheral myelin protein 22 (PMP22) deletion and the other case showed a previously reported single base pair deletion at Leu145 causing a frameshift mutation at the PMP22 gene. These cases underscore the difficulty of diagnosing HNPP, because of the variations in clinical and electrophysiological findings and reinforce the importance of a combination high index of clinical suspicion, electrodiagnostic testing, and genetic testing to make the diagnosis.

26 CFR 1.752-2 - Partner's share of recourse liabilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., unless the facts and circumstances indicate a plan to circumvent or avoid the obligation. See paragraphs... Other than the partners' obligation to fund negative capital accounts on liquidation, there are no other... circumvent or avoid E's obligation to contribute to the partnership. Example 4. Partner guarantee with right...

46 CFR 204.9 - Indemnity or contribution.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the United States. If a claim arises under circumstances in which the United States is entitled to... party to honor its obligation to the United States or to accept its share of joint liability. If the...) Sought from the United States. Claims for indemnity or contribution from the United States shall be...

46 CFR 204.9 - Indemnity or contribution.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the United States. If a claim arises under circumstances in which the United States is entitled to... party to honor its obligation to the United States or to accept its share of joint liability. If the...) Sought from the United States. Claims for indemnity or contribution from the United States shall be...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

7 CFR 1427.175 - Liability of the producer.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Recourse Seed Cotton Loans § 1427.175... addition, seed cotton pledged as collateral for such loan shall not be released to the producer until such... repaid without regard to such producer's claimed share in the seed cotton pledged as collateral for the...

26 CFR 1.752-2 - Partner's share of recourse liabilities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of present value. The present value of the guaranteed future interest payments is computed using a... interest index, the present value is computed on the assumption that the interest determined under the... first foreclosing on the property. When the partnership obtains the loan, the present value (discounted...

26 CFR 1.752-2 - Partner's share of recourse liabilities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... of present value. The present value of the guaranteed future interest payments is computed using a... interest index, the present value is computed on the assumption that the interest determined under the... first foreclosing on the property. When the partnership obtains the loan, the present value (discounted...

26 CFR 1.752-2 - Partner's share of recourse liabilities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of present value. The present value of the guaranteed future interest payments is computed using a... interest index, the present value is computed on the assumption that the interest determined under the... first foreclosing on the property. When the partnership obtains the loan, the present value (discounted...

26 CFR 1.752-2 - Partner's share of recourse liabilities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of present value. The present value of the guaranteed future interest payments is computed using a... interest index, the present value is computed on the assumption that the interest determined under the... first foreclosing on the property. When the partnership obtains the loan, the present value (discounted...

The Development and Implementation of Outdoor-Based Secondary School Integrated Programs

ERIC Educational Resources Information Center

Comishin, Kelly; Dyment, Janet E.; Potter, Tom G.; Russell, Constance L.

2004-01-01

Four teachers share the challenges they faced when creating and running outdoor-focused secondary school integrated programs in British Columbia, Canada. The five most common challenges were funding constraints, insufficient support from administrators and colleagues, time constraints, liability and risk management, and inadequate skills and…

Evidence that genetic variation in the oxytocin receptor (OXTR) gene influences social cognition in ADHD.

PubMed

Park, J; Willmott, M; Vetuz, G; Toye, C; Kirley, A; Hawi, Z; Brookes, K J; Gill, M; Kent, L

2010-05-30

Some children with ADHD also have social and communication difficulties similar to those seen in children with autistic spectrum disorders and this may be due to shared genetic liability. As the oxytocin receptor (OXTR) gene has been implicated in social cognition and autistic spectrum disorders, this study investigated whether OXTR polymorphisms previously implicated in autism were associated with ADHD and whether they influenced OXTR mRNA expression in 27 normal human amygdala brain samples. The family-based association sample consisted of 450 DSM-IV diagnosed ADHD probands and their parents. Although there was no association with the ADHD phenotype, an association with social cognitive impairments in a subset of the ADHD probands (N=112) was found for SNP rs53576 (F=5.24, p=0.007) with post-hoc tests demonstrating that the AA genotype was associated with better social ability compared to the AG genotype. Additionally, significant association was also found for rs13316193 (F=3.09, p=0.05) with post-hoc tests demonstrating that the CC genotype was significantly associated with poorer social ability than the TT genotype. No significant association between genotype and OXTR mRNA expression was found. This study supports previous evidence that the OXTR gene is implicated in social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

The CCC2000 Birth Cohort Study of Register-Based Family History of Mental Disorders and Psychotic Experiences in Offspring

PubMed Central

Jeppesen, Pia; Larsen, Janne Tidselbak; Clemmensen, Lars; Munkholm, Anja; Rimvall, Martin Kristian; Rask, Charlotte Ulrikka; van Os, Jim; Petersen, Liselotte; Skovgaard, Anne Mette

2015-01-01

Psychotic experiences (PE) in individuals of the general population are hypothesized to mark the early expression of the pathology underlying psychosis. This notion of PE as an intermediate phenotype is based on the premise that PE share genetic liability with psychosis. We examined whether PE in childhood was predicted by a family history of mental disorder with psychosis rather than a family history of nonpsychotic mental disorder and whether this association differed by severity of PE. The study examined data on 1632 children from a general population birth cohort assessed at age 11–12 years by use of a semistructured interview covering 22 psychotic symptoms. The Danish national registers were linked to describe the complete family history of hospital-based psychiatric diagnoses. Uni- and multivariable logistic regressions were used to test whether a family history of any mental disorder with psychosis, or of nonpsychotic mental disorder, vs no diagnoses was associated with increased risk of PE in offspring (hierarchical exposure variable). The occurrence of PE in offspring was significantly associated with a history of psychosis among the first-degree relatives (adjusted relative risk [RR] = 3.29, 95% CI: 1.82–5.93). The risk increased for combined hallucinations and delusions (adjusted RR = 5.90, 95% CI: 2.64–13.16). A history of nonpsychotic mental disorders in first-degree relatives did not contribute to the risk of PE in offspring nor did any mental disorder among second-degree relatives. Our findings support the notion of PE as a vulnerability marker of transdiagnostic psychosis. The effect of psychosis in first-degree relatives may operate through shared genetic and environmental factors. PMID:25452427

Familial resemblance and shared latent familial variance in recurrent fall risk in older women

PubMed Central

Cauley, Jane A.; Roth, Stephen M.; Kammerer, Candace; Stone, Katie; Hillier, Teresa A.; Ensrud, Kristine E.; Hochberg, Marc; Nevitt, Michael C.; Zmuda, Joseph M.

2010-01-01

Background: A possible familial component to fracture risk may be mediated through a genetic liability to fall recurrently. Methods: Our analysis sample included 186 female sibling-ships (n = 401) of mean age 71.9 yr (SD = 5.0). Using variance component models, we estimated residual upper-limit heritabilities in fall-risk mobility phenotypes (e.g., chair-stand time, rapid step-ups, and usual-paced walking speed) and in recurrent falls. We also estimated familial and environmental (unmeasured) correlations between pairs of fall-risk mobility phenotypes. All models were adjusted for age, height, body mass index, and medical and environmental factors. Results: Residual upper-limit heritabilities were all moderate (P < 0.05), ranging from 0.27 for usual-paced walking speed to 0.58 for recurrent falls. A strong familial correlation between usual-paced walking speed and rapid step-ups of 0.65 (P < 0.01) was identified. Familial correlations between usual-paced walking speed and chair-stand time (−0.02) and between chair-stand time and rapid step-ups (−0.27) were both nonsignificant (P > 0.05). Environmental correlations ranged from 0.35 to 0.58 (absolute values), P < 0.05 for all. Conclusions: There exists moderate familial resemblance in fall-risk mobility phenotypes and recurrent falls among older female siblings, which we expect is primarily genetic given that adult siblings live separate lives. All fall-risk mobility phenotypes may be coinfluenced at least to a small degree by shared latent familial or environmental factors; however, up to approximately one-half of the covariation between usual-paced walking speed and rapid step-ups may be due to a common set of genes. PMID:20167680

Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement.

PubMed

Carey, Caitlin E; Agrawal, Arpana; Bucholz, Kathleen K; Hartz, Sarah M; Lynskey, Michael T; Nelson, Elliot C; Bierut, Laura J; Bogdan, Ryan

2016-01-01

Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium's Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the five psychiatric disorders which comprised CROSS-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)-and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p < 0.001). After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: (A) MDD PRS and non-problem cannabis use, (B) MDD PRS and severe cocaine dependence, (C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and (D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

PubMed Central

Wheeler, William A.; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I.; Lan, Qing; Abnet, Christian C.; Amundadottir, Laufey T.; Figueroa, Jonine D.; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A.; Taylor, Philip R.; Vivo, Immaculata De; McGlynn, Katherine A.; Purdue, Mark P.; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Angelucci, Emanuele; Ansell, Stephen M.; Arici, Cecilia; Armstrong, Bruce K.; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A.; Birmann, Brenda M.; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brinton, Louise; Brooks-Wilson, Angela R.; Bueno-de-Mesquita, H. Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K. C.; Chang, Ellen T.; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C.; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S.; Comperat, Eva; Conde, Lucia; Connors, Joseph M.; Conti, David; Cortessis, Victoria K.; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G.; Ding, Ti; Diver, W. Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J.; Ennas, Maria Grazia; Erickson, Ralph L.; Feychting, Maria; Flanagan, Adrienne M.; Foretova, Lenka; Fraumeni, Joseph F.; Freedman, Neal D.; Beane Freeman, Laura E.; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D.; Gastier-Foster, Julie; Gaudet, Mia M.; Gaziano, J. Michael; Giffen, Carol; Giles, Graham G.; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M.; Haiman, Christopher A.; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R.; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Horn-Ross, Pamela L.; Hosain, G. M. Monawar; Hosgood, H. Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D.; Jackson, Rebecca D.; Jacobs, Eric J.; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R.; Kelly, Rachel S.; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert J.; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M.; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S.; Link, Brian K.; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Lollo, Simonetta Di; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Marchand, Loic Le; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S.; Michaud, Dominique S.; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E.; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Oberg, Ann L.; Offit, Kenneth; Oh, In-Jae; Olson, Sara H.; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A.; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M.; de Sanjose, Silvia; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K.; Shanafelt, Tait D.; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Spinelli, John J.; Staines, Anthony; Stampfer, Meir; Stern, Marianna C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael S.; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A.; Tinker, Lesley F.; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C.; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C. H.; Villano, Danylo J.; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J.; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M.; Cerhan, James R.; Ferri, Giovanni M.; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M.; Smedby, Karin E.; Teras, Lauren R.; Vijai, Joseph; Wang, Sophia S.; Brennan, Paul; Caporaso, Neil E.; Hunter, David J.; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T.; Slager, Susan L.; Chanock, Stephen J.; Chatterjee, Nilanjan

2015-01-01

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl 2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. PMID:26464424

Th17/T regulator cell balance and NK cell numbers in relation to psychosis liability and social stress reactivity.

PubMed

Counotte, J; Drexhage, H A; Wijkhuijs, J M; Pot-Kolder, R; Bergink, V; Hoek, H W; Veling, W

2018-03-01

Psychotic disorders are characterized by a deranged immune system, including altered number and function of Natural Killer (NK) and T cells. Psychotic disorders arise from an interaction between genetic vulnerability and exposure to environmental risk factors. Exposure to social adversity during early life is particularly relevant to psychosis risk and is thought to increase reactivity to subsequent minor daily social stressors. Virtual reality allows controlled experimental exposure to virtual social stressors. To investigate the interplay between social adversity during early life, cell numbers of NK cells and T helper subsets and social stress reactivity in relation to psychosis liability. Circulating numbers of Th1, Th2, Th17, T regulator and NK cells were determined using flow cytometry in 80 participants with low psychosis liability (46 healthy controls and 34 siblings) and 53 participants with high psychosis liability (14 ultra-high risk (UHR) patients and 39 recent-onset psychosis patients), with and without the experience of childhood trauma. We examined if cell numbers predicted subjective stress when participants were exposed to social stressors (crowdedness, hostility and being part of an ethnic minority) in a virtual reality environment. There were no significant group differences in Th1, Th2, Th17, T regulator and NK cell numbers between groups with a high or low liability for psychosis. However, in the high psychosis liability group, childhood trauma was associated with increased Th17 cell numbers (p = 0.028). Moreover, in the high psychosis liability group increased T regulator and decreased NK cell numbers predicted stress experience during exposure to virtual social stressors (p = 0.015 and p = 0.009 for T regulator and NK cells, respectively). A deranged Th17/T regulator balance and a reduced NK cell number are associated intermediate biological factors in the relation childhood trauma, psychosis liability and social stress reactivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Integrating Social Science and Behavioral Genetics: Testing the Origin of Socioeconomic Disparities in Depression Using a Genetically Informed Design

PubMed Central

Myers, John M.; Kendler, Kenneth S.

2013-01-01

Objectives. We tested 3 hypotheses—social causation, social drift, and common cause—regarding the origin of socioeconomic disparities in major depression and determined whether the relationship between socioeconomic status (SES) and major depression varied by genetic liability for major depression. Methods. Data were from a sample of female twins in the baseline Virginia Adult Twin Study of Psychiatric and Substance Use Disorders interviewed between 1987 and 1989 (n = 2153). We used logistic regression and structural equation twin models to evaluate these 3 hypotheses. Results. Consistent with the social causation hypothesis, education (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.66, 0.93; P < .01) and income (OR = 0.93; 95% CI = 0.89, 0.98; P < .01) were significantly related to past-year major depression. Upward social mobility was associated with lower risk of depression. There was no evidence that childhood SES was related to development of major depression (OR = 0.98; 95% CI = 0.89, 1.09; P > .1). Consistent with a common genetic cause, there was a negative correlation between the genetic components of major depression and education (r2 =  –0.22). Co-twin control analyses indicated a protective effect of education and income on major depression even after accounting for genetic liability. Conclusions. This study utilized a genetically informed design to address how social position relates to major depression. Results generally supported the social causation model. PMID:23927513

17 CFR 260.0-11 - Liability for certain statements by issuers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (loss), earnings (loss) per share, capital expenditures, dividends, capital structure or other financial...) At the time such statements are made or reaffirmed, either the issuer is subject to the reporting... subject to the reporting requirements of section 13(a) or 15(d) of the Securities Exchange Act of 1934...

17 CFR 260.0-11 - Liability for certain statements by issuers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (loss), earnings (loss) per share, capital expenditures, dividends, capital structure or other financial...) At the time such statements are made or reaffirmed, either the issuer is subject to the reporting... subject to the reporting requirements of section 13(a) or 15(d) of the Securities Exchange Act of 1934...

75 FR 33306 - Change in Bank Control Notices; Acquisition of Shares of Bank or Bank Holding Companies

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

...., a Delaware limited partnership; Tailwind Capital Partners (PP), L.P., a Delaware limited partnership; Tailwind Capital Partners, L.P., a Delaware limited partnership; Tailwind Capital Partners (ERISA), L.P., a Delaware limited partnership; Tailwind HSB Holdings, LLC, a Delaware limited liability company; Tailwind...

26 CFR 1.1446-2 - Determining a partnership's effectively connected taxable income allocable to foreign partners...

Code of Federal Regulations, 2010 CFR

2010-04-01

... pro-rata share of the partnership's assets and liabilities for these purposes. For these purposes, the... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Determining a partnership's effectively....1446-2 Determining a partnership's effectively connected taxable income allocable to foreign partners...

26 CFR 1.404(g)-1 - Deduction of employer liability payments.

Code of Federal Regulations, 2010 CFR

2010-04-01

...(g)-1 Section 1.404(g)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.404(g)-1... employer. (c) Limitations, etc.—(1) Permissible expenses. A payment shall be deductible under section 404(g...

78 FR 78255 - Shared Responsibility Payment for Not Maintaining Minimum Essential Coverage; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... amendments: PART 1--INCOME TAXES 0 Paragraph 1. The authority citation for part 1 is amended by correcting... final regulations provide guidance to individual taxpayers on the liability under section 5000A of the... clarification. List of Subjects in 26 CFR Part 1 Income taxes, Reporting and recordkeeping requirements...

Impact of Critical Access Hospital Conversion on Beneficiary Liability

ERIC Educational Resources Information Center

Gilman, Boyd H.

2008-01-01

Context: While the Medicare Critical Access Hospital (CAH) program has improved the financial viability of small rural hospitals and enhanced access to care in rural communities, the program puts beneficiaries at risk for paying a larger share of the cost of services covered under the Medicare part B benefit. Purpose: This paper examines the…

Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects

PubMed Central

Thapar, Anita; Harold, Gordon; Rice, Frances; Ge, XiaoJia; Boivin, Jacky; Hay, Dale; van den Bree, Marianne; Lewis, Allyson

2007-01-01

Background There is much evidence to suggest that risk for common clinical disorders begins in foetal life. Exposure to environmental risk factors however is often not random. Many commonly used indices of prenatal adversity (e.g. maternal gestational stress, gestational diabetes, smoking in pregnancy) are influenced by maternal genes and genetically influenced maternal behaviour. As mother provides the baby with both genes and prenatal environment, associations between prenatal risk factors and offspring disease maybe attributable to true prenatal risk effects or to the "confounding" effects of genetic liability that are shared by mother and offspring. Cross-fostering designs, including those that involve embryo transfer have proved useful in animal studies. However disentangling these effects in humans poses significant problems for traditional genetic epidemiological research designs. Methods We present a novel research strategy aimed at disentangling maternally provided pre-natal environmental and inherited genetic effects. Families of children aged 5 to 9 years born by assisted reproductive technologies, specifically homologous IVF, sperm donation, egg donation, embryo donation and gestational surrogacy were contacted through fertility clinics and mailed a package of questionnaires on health and mental health related risk factors and outcomes. Further data were obtained from antenatal records. Results To date 741 families from 18 fertility clinics have participated. The degree of association between maternally provided prenatal risk factor and child outcome in the group of families where the woman undergoing pregnancy and offspring are genetically related (homologous IVF, sperm donation) is compared to association in the group where offspring are genetically unrelated to the woman who undergoes the pregnancy (egg donation, embryo donation, surrogacy). These comparisons can be then examined to infer the extent to which prenatal effects are genetically and environmentally mediated. Conclusion A study based on children born by IVF treatment and who differ in genetic relatedness to the woman undergoing the pregnancy is feasible. The present report outlines a novel experimental method that permits disaggregation of maternally provided inherited genetic and post-implantation prenatal effects. PMID:17587444

THE EVOLUTION OF RESISTANCE TO PLANT INCORPORATED PROTECTANTS BY TARGETED INSECT PESTS

EPA Science Inventory

Genetically modified (GM) crops, also known as transgenic crops, offer potential economic, environmental, and human health benefits. Balanced against these potential benefits are several possible liabilities, one of which is environmental harm. The EPA must fulfill its mandate to...

Promoting Physical Activity Through the Shared Use of School Recreational Spaces: A Policy Statement From the American Heart Association

PubMed Central

Young, Deborah R.; Spengler, John O.; Frost, Natasha; Evenson, Kelly R.; Vincent, Jeffrey M.; Whitsel, Laurie

2014-01-01

Most Americans are not sufficiently physically active, even though regular physical activity improves health and reduces the risk of many chronic diseases. Those living in rural, non-White, and lower-income communities often have insufficient access to places to be active, which can contribute to their lower level of physical activity. The shared use of school recreational facilities can provide safe and affordable places for communities. Studies suggest that challenges to shared use include additional cost, liability protection, communication among constituencies interested in sharing space, and decision-making about scheduling and space allocation. This American Heart Association policy statement has provided recommendations for federal, state, and local decision-makers to support and expand opportunities for physical activity in communities through the shared use of school spaces. PMID:24134355

Promoting physical activity through the shared use of school recreational spaces: a policy statement from the American Heart Association.

PubMed

Young, Deborah R; Spengler, John O; Frost, Natasha; Evenson, Kelly R; Vincent, Jeffrey M; Whitsel, Laurie

2014-09-01

Most Americans are not sufficiently physically active, even though regular physical activity improves health and reduces the risk of many chronic diseases. Those living in rural, non-White, and lower-income communities often have insufficient access to places to be active, which can contribute to their lower level of physical activity. The shared use of school recreational facilities can provide safe and affordable places for communities. Studies suggest that challenges to shared use include additional cost, liability protection, communication among constituencies interested in sharing space, and decision-making about scheduling and space allocation. This American Heart Association policy statement has provided recommendations for federal, state, and local decision-makers to support and expand opportunities for physical activity in communities through the shared use of school spaces.

Globalisation, environmental harm, and progress: the role of consensus and liability.

PubMed

Zandvoort, H

2005-01-01

Two conditions are stated that must be fulfilled to make sure that the negative effects of environmental pollution and risks stemming from the spread of free markets and technology do not outweigh the beneficial effects of this development. (1) For all activities, all those who may experience the negative effects of the activities must have given their consent to the activities and the conditions under which they are performed. (2) Those who engage in activities without this consent must be held to unlimited and unconditional liability for the negative effects that the activities may cause for those who did not give their consent. These conditions are necessary principles for the responsible management of environmental harm and risks. If the conditions are not satisfied, then the belief that the global spread of free markets and technology is beneficial for all, or does not harm anyone, cannot be justified. Neither of the conditions is fulfilled at present. This is illustrated using examples drawn from international legislation regarding liability for oil transportation, energy production, genetically modified organisms and chemicals in the environment. Directions for improving existing liability legislation are identified. The relationship between the conditions and the precautionary principle is explained.

The familial co-aggregation of ASD and ADHD: a register-based cohort study.

PubMed

Ghirardi, L; Brikell, I; Kuja-Halkola, R; Freitag, C M; Franke, B; Asherson, P; Lichtenstein, P; Larsson, H

2018-02-01

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77-22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80-32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21-5.85) and full siblings (OR=4.59, 95% CI: 4.39-4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.

Genetic liability for schizophrenia predicts risk of immune disorders.

PubMed

Stringer, Sven; Kahn, René S; de Witte, Lot D; Ophoff, Roel A; Derks, Eske M

2014-11-01

Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap between schizophrenia and three immune disorders and to compare with the overlap between schizophrenia and two disorders not primarily characterized by immune dysregulation: bipolar disorder and type 2 diabetes. We performed a polygenic risk score analysis using results from the schizophrenia Psychiatric GWAS consortium (PGC) (8922 cases and 9528 controls) and five Wellcome Trust Case Control Consortium (WTCCC) case samples as target cases: bipolar disorder (n=1998), type 1 diabetes (n=2000), Crohn's diseases (n=2005), rheumatoid arthritis (n=1999), and type 2 diabetes (n=1999). The WTCCC British Birth Cohort and National Blood Service samples (n=3004) were used as target controls. Additionally, we tested whether schizophrenia polygenic risk scores significantly differed between patients with immune disorder, bipolar disorder, and type 2 diabetes respectively. Polygenic risk scores for schizophrenia significantly predicted disease status in all three immune disorder samples (Nagelkerke-R(2) 1.1%-1.3%; p<0.05). The polygenic risk of schizophrenia in patients with immune disorders was significantly lower than in patients with bipolar disorder (Nagelkerke-R(2) 6.0%; p<0.05), but higher than in type 2 diabetes patients (Nagelkerke-R(2) 0.5%; p<0.05). Our results suggest that genetic factors are shared between schizophrenia and immune disorders. This contributes to an accumulating body of evidence that immune processes may play a role in the etiology of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Parental depression and offspring psychopathology: a children of twins study.

PubMed

Singh, A L; D'Onofrio, B M; Slutske, W S; Turkheimer, E; Emery, R E; Harden, K P; Heath, A C; Madden, P A F; Statham, D J; Martin, N G

2011-07-01

Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Abdominal obesity and circulating metabolites: A twin study approach.

PubMed

Bogl, Leonie H; Kaye, Sanna M; Rämö, Joel T; Kangas, Antti J; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietiläinen, Kirsi H

2016-03-01

To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (rg) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference ≥3 kg/m(2)). Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic and environmental risk for major depression in African-American and European-American women.

PubMed

Duncan, Alexis E; Munn-Chernoff, Melissa A; Hudson, Darrell L; Eschenbacher, Michaela A; Agrawal, Arpana; Grant, Julia D; Nelson, Elliot C; Waldron, Mary; Glowinski, Anne L; Sartor, Carolyn E; Bucholz, Kathleen K; Madden, Pamela A F; Heath, Andrew C

2014-08-01

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18-28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67-1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29-78% vs. 41%, 95% CI: 29-52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33-53% and E = 57%, 47-67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women.

A legal framework to enable sharing of Clinical Decision Support knowledge and services across institutional boundaries.

PubMed

Hongsermeier, Tonya; Maviglia, Saverio; Tsurikova, Lana; Bogaty, Dan; Rocha, Roberto A; Goldberg, Howard; Meltzer, Seth; Middleton, Blackford

2011-01-01

The goal of the CDS Consortium (CDSC) is to assess, define, demonstrate, and evaluate best practices for knowledge management and clinical decision support in healthcare information technology at scale - across multiple ambulatory care settings and Electronic Health Record technology platforms. In the course of the CDSC research effort, it became evident that a sound legal foundation was required for knowledge sharing and clinical decision support services in order to address data sharing, intellectual property, accountability, and liability concerns. This paper outlines the framework utilized for developing agreements in support of sharing, accessing, and publishing content via the CDSC Knowledge Management Portal as well as an agreement in support of deployment and consumption of CDSC developed web services in the context of a research project under IRB oversight.

Increasing Liability Premiums in Obstetrics - Analysis, Effects and Options.

PubMed

Soergel, P; Schöffski, O; Hillemanns, P; Hille-Betz, U; Kundu, S

2015-04-01

Whenever people act, mistakes are made. In Germany, it is thought that a total of 40 000 cases of malpractice occur per year. In recent years, costs for liability insurance have risen significantly in almost all spheres of medicine as a whole. Liability in the health care sector is founded on the contractual relationship between doctor and patient. Most recently, case law developed over many years has been codified with the Patients' Rights Act. In obstetrics, the focus of liability law is on brain damage caused by hypoxia or ischemia as a result of management errors during birth. The costs per claim are made up of various components together with different shares of damage costs (increased needs, in particular therapy costs and nursing fees, acquisition damage, treatment costs, compensation). In obstetrics in particular, recent focus has been on massively increased liability payments, also accompanied by higher liability premiums. This causes considerable financial burdens on hospitals as well as on midwives and attending physicians. The premiums are so high, especially for midwives and attending physicians, that professional practice becomes uneconomical in some cases. In recent years, these circumstances have also been intensely debated in the public sphere and in politics. However, the focus here is on the occupation of midwife. In 2014, in the GKV-FQWG (Statutory Health Insurance - Quality and Further Development Act), a subsidy towards the occupational liability premium was defined for midwives who only attended a few deliveries. However, to date, a complete solution to the problem has not been found. A birth will never be a fully controllable risk, but in rare cases will always end with injury to the child. The goal must be to minimise this risk, through good education and continuous training, as well as constant critical analysis of one's own activities. Furthermore, it seems sensible, especially in non-clinical Obstetrics, to look at the current study data more closely. Among the many solutions which have been proposed, such as the development of quality management, risk management and prevention, better remuneration, a waiver on recourse claims by social insurance underwriters, a cap on damage costs of liability insurers, state liability, an indemnity fund, a system change to Medical Treatment Risk Insurance, as well as a discussion on whether or not it makes sense to use non-clinical obstetrics for the prevention of a further increase in premiums, not one stands out as being especially convincing. On the contrary, a meaningful coordination of various concepts should follow. What seems sensible is a higher remuneration per birth, taking into account the liability premiums as well as, in the medium term, the establishment of a liability fund which, from a certain limit upwards, steps in as liable third party.

Increasing Liability Premiums in Obstetrics – Analysis, Effects and Options

PubMed Central

Soergel, P.; Schöffski, O.; Hillemanns, P.; Hille-Betz, U.; Kundu, S.

2015-01-01

Whenever people act, mistakes are made. In Germany, it is thought that a total of 40 000 cases of malpractice occur per year. In recent years, costs for liability insurance have risen significantly in almost all spheres of medicine as a whole. Liability in the health care sector is founded on the contractual relationship between doctor and patient. Most recently, case law developed over many years has been codified with the Patientsʼ Rights Act. In obstetrics, the focus of liability law is on brain damage caused by hypoxia or ischemia as a result of management errors during birth. The costs per claim are made up of various components together with different shares of damage costs (increased needs, in particular therapy costs and nursing fees, acquisition damage, treatment costs, compensation). In obstetrics in particular, recent focus has been on massively increased liability payments, also accompanied by higher liability premiums. This causes considerable financial burdens on hospitals as well as on midwives and attending physicians. The premiums are so high, especially for midwives and attending physicians, that professional practice becomes uneconomical in some cases. In recent years, these circumstances have also been intensely debated in the public sphere and in politics. However, the focus here is on the occupation of midwife. In 2014, in the GKV-FQWG (Statutory Health Insurance – Quality and Further Development Act), a subsidy towards the occupational liability premium was defined for midwives who only attended a few deliveries. However, to date, a complete solution to the problem has not been found. A birth will never be a fully controllable risk, but in rare cases will always end with injury to the child. The goal must be to minimise this risk, through good education and continuous training, as well as constant critical analysis of oneʼs own activities. Furthermore, it seems sensible, especially in non-clinical Obstetrics, to look at the current study data more closely. Among the many solutions which have been proposed, such as the development of quality management, risk management and prevention, better remuneration, a waiver on recourse claims by social insurance underwriters, a cap on damage costs of liability insurers, state liability, an indemnity fund, a system change to Medical Treatment Risk Insurance, as well as a discussion on whether or not it makes sense to use non-clinical obstetrics for the prevention of a further increase in premiums, not one stands out as being especially convincing. On the contrary, a meaningful coordination of various concepts should follow. What seems sensible is a higher remuneration per birth, taking into account the liability premiums as well as, in the medium term, the establishment of a liability fund which, from a certain limit upwards, steps in as liable third party. PMID:26028694

Turning the Potential Liability of Large Enrollment Laboratory Science Courses into an Asset

ERIC Educational Resources Information Center

Johnson, Dan; Levy, Foster; Karsai, Istvan; Stroud, Kimberly

2006-01-01

Data sharing among multiple lab sections increases statistical power of data analyses and informs student-generated hypotheses. We describe how to collect, organize, and manage data to support replicate and rolling inquiry models, with three illustrative examples of activities from a population-level biology course for science majors. (Contains 1…

26 CFR 1.1248-4 - Limitation on tax applicable to individuals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... example: Example: On December 31, 1966, Smith, a United States person, sells a share of stock of X... in his gross income as a dividend under section 1248(a). Both X and Smith use the calendar year as the taxable year. The increase in Smith's income tax liability for 1966 which is attributable (under...

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics

PubMed Central

Lee, Sandra Soo-Jin; Vernez, Simone L.; Ormond, K.E.; Granovetter, Mark

2013-01-01

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Methods: Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. Results: 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Conclusion: Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities. PMID:25562728

Attitudes towards Social Networking and Sharing Behaviors among Consumers of Direct-to-Consumer Personal Genomics.

PubMed

Lee, Sandra Soo-Jin; Vernez, Simone L; Ormond, K E; Granovetter, Mark

2013-10-14

Little is known about how consumers of direct-to-consumer personal genetic services share personal genetic risk information. In an age of ubiquitous online networking and rapid development of social networking tools, understanding how consumers share personal genetic risk assessments is critical in the development of appropriate and effective policies. This exploratory study investigates how consumers share personal genetic information and attitudes towards social networking behaviors. Adult participants aged 23 to 72 years old who purchased direct-to-consumer genetic testing from a personal genomics company were administered a web-based survey regarding their sharing activities and social networking behaviors related to their personal genetic test results. 80 participants completed the survey; of those, 45% shared results on Facebook and 50.9% reported meeting or reconnecting with more than 10 other individuals through the sharing of their personal genetic information. For help interpreting test results, 70.4% turned to Internet websites and online sources, compared to 22.7% who consulted their healthcare providers. Amongst participants, 51.8% reported that they believe the privacy of their personal genetic information would be breached in the future. Consumers actively utilize online social networking tools to help them share and interpret their personal genetic information. These findings suggest a need for careful consideration of policy recommendations in light of the current ambiguity of regulation and oversight of consumer initiated sharing activities.

[Medicolegal aspects in neuroradiologic emergencies].

PubMed

Picard, L

2004-09-01

Naturally, neuroimaging emergencies are a component of the global subject of emergencies that have for several years been a frequent subject in the press. The current situation is the consequence of the evolution of ideas from contractual liability to the frequently discussed principle of precaution. Examples offered by the daily practice allow to emphasize the main difficulties: diagnosis of headaches, seizure episode on public roads, head trauma, stroke... The medical liability of the neuroradiologist is not the same for diagnostic or interventional neuroradiology; it can sometimes be shared with other physicians. This liability includes the indication, the quality of the diagnosis, the information of the patient and relatives, the communication of results with other physicians, the maintenance of the equipment... Knowledge of potential pitfalls allows preventive measures including competence of the neuroradiologist, informed patient consent, and written precise protocols are the most important. However, according to the evolution of our societies, it is likely that it will become increasingly difficult to achieve a professional neuroradiology career without being questioned; it is thus advisable to be prepared for such eventuality.

Drug-Induced Psychosis: How to Avoid Star Gazing in Schizophrenia Research by Looking at More Obvious Sources of Light

PubMed Central

Paparelli, Alessandra; Di Forti, Marta; Morrison, Paul D.; Murray, Robin M.

2010-01-01

The prevalent view today is that schizophrenia is a syndrome rather than a specific disease. Liability to schizophrenia is highly heritable. It appears that multiple genetic and environmental factors operate together to push individuals over a threshold into expressing the characteristic clinical picture. One environmental factor which has been curiously neglected is the evidence that certain drugs can induce schizophrenia-like psychosis. In the last 60 years, improved understanding of the relationship between drug abuse and psychosis has contributed substantially to our modern view of the disorder suggesting that liability to psychosis in general, and to schizophrenia in particular, is distributed trough the general population in a similar continuous way to liability to medical disorders such as hypertension and diabetes. In this review we examine the main hypotheses resulting from the link observed between the most common psychotomimetic drugs (lysergic acid diethylamide, amphetamines, cannabis, phencyclidine) and schizophrenia. PMID:21267359

Models of comorbidity for multifactorial disorders.

PubMed Central

Neale, M C; Kendler, K S

1995-01-01

We develop several formal models for comorbidity between multifactorial disorders. Based on the work of D. N. Klein and L. P. Riso, the models include (i) alternate forms, where the two disorders have the same underlying continuum of liability; (ii) random multiformity, in which affection status on one disorder abruptly increases risk for the second; (iii) extreme multiformity, where only extreme cases have an abruptly increased risk for the second disorder; (iv) three independent disorders, in which excess comorbid cases are due to a separate, third disorder; (v) correlated liabilities, where the risk factors for the two disorders correlate; and (vi) direct causal models, where the liability for one disorder is a cause of the other disorder. These models are used to make quantitative predictions about the relative proportions of pairs of relatives who are classified according to whether each relative has neither disorder, disorder A but not B, disorder B but not A, or both A and B. For illustration, we analyze data on major depression (MD) and generalized anxiety disorder (GAD) assessed in adult female MZ and DZ twins, which enable estimation of the relative impact of genetic and environmental factors. Several models are rejected--that comorbid cases are due to chance; multiformity of GAD; a third independent disorder; and GAD being a cause of MD. Of the models that fit the data, correlated liabilities, MD causes GAD, and reciprocal causation seem best. MD appears to be a source of liability for GAD. Possible extensions to the models are discussed. PMID:7573055

Direct to confusion: lessons learned from marketing BRCA testing.

PubMed

Matloff, Ellen; Caplan, Arthur

2008-06-01

Myriad Genetics holds a patent on testing for the hereditary breast and ovarian cancer genes, BRCA1 and BRCA2, and therefore has a forced monopoly on this critical genetic test. Myriad launched a Direct-to-Consumer (DTC) marketing campaign in the Northeast United States in September 2007 and plans to expand that campaign to Florida and Texas in 2008. The ethics of Myriad's patent, forced monopoly and DTC campaign will be reviewed, as well as the impact of this situation on patient access and care, physician liability, and the future of DTC campaigns for genetic testing.

The MAOA promoter polymorphism, disruptive behavior disorders, and early onset substance use disorder: gene-environment interaction.

PubMed

Vanyukov, Michael M; Maher, Brion S; Devlin, Bernie; Kirillova, Galina P; Kirisci, Levent; Yu, Ling-Mei; Ferrell, Robert E

2007-12-01

Conduct, oppositional defiant, and attention deficit hyperactivity disorders, reflecting early antisociality and behavior dysregulation, are predictive of substance use disorders. Liabilities to these disorders share genetic and environmental variance. Parenting characteristics have been shown to influence development of antisociality, moderated by variation at the MAOA gene, which has also been associated with the risk for substance use disorders. To extend these findings, we tested the relationships between the MAOA promoter polymorphism (variable number tandem repeat), indices of child's perception of paternal and maternal parenting, and disruptive behavior disorders and substance use disorders. A sample of 148 European-American males was assessed prospectively at ages from 10-12 to 18-19 years and genotyped for the monoamine oxidase A variable number tandem repeat. The Diagnostic and statistical manual of mental disorder-III-R diagnoses were obtained using standard methodology. Parenting was assessed using a scale summarizing the child's evaluation of the parenting style (parent's behavior toward him, parental emotional distance and involvement). Correlation, logistic regression, and Cox proportional hazard regression analysis was used to determine the relationships between the variables. The strength of association between parenting index and conduct and attention deficit hyperactivity disorders depended on the MAOA genotype. Unlike earlier findings, the parenting-risk relationships were observed in the 'high-' rather than 'low-activity' genotypes. The strength and direction of relationships depended on the parental sex. The MAOA polymorphism's association with the risk for substance use disorders was detected when parenting was controlled for. The results are consistent with the contribution of the MAOA gene, parenting style and their interactions to variation in the risk for early onset behavior disorders and liability to substance use disorders.

Social and Emotional Adjustment of Siblings of Children with Autism

ERIC Educational Resources Information Center

Pilowsky, Tammy; Yirmiya, Nurit; Doppelt, Osnat; Gross-Tsur, Varda; Shalev, Ruth S.

2004-01-01

Background: Social and emotional adjustment of siblings of children with autism was examined, to explore their risk or resilience to effects of genetic liability and environmental factors involved in having a sibling with autism. Method: Social-emotional adjustment, behavior problems, socialization skills, and siblings' relationships were compared…

Expression of the Broad Autism Phenotype in Simplex Autism Families from the Simons Simplex Collection

ERIC Educational Resources Information Center

Davidson, Julie; Goin-Kochel, Robin P.; Green-Snyder, Lee Anne; Hundley, Rachel J.; Warren, Zachary; Peters, Sarika U.

2014-01-01

The broad autism phenotype (BAP) refers to the phenotypic expression of an underlying genetic liability to autism, manifest in non-autistic relatives. This study examined the relationship among the "Broad Autism Phenotype Questionnaire" (BAPQ), "Social Responsiveness Scale: Adult Research Version" (SRS:ARV), and "Family…

The Broad Autism Phenotype Questionnaire

ERIC Educational Resources Information Center

Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

2007-01-01

The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

Quantitative genetics of disease traits.

PubMed

Wray, N R; Visscher, P M

2015-04-01

John James authored two key papers on the theory of risk to relatives for binary disease traits and the relationship between parameters on the observed binary scale and an unobserved scale of liability (James Annals of Human Genetics, 1971; 35: 47; Reich, James and Morris Annals of Human Genetics, 1972; 36: 163). These two papers are John James' most cited papers (198 and 328 citations, November 2014). They have been influential in human genetics and have recently gained renewed popularity because of their relevance to the estimation of quantitative genetics parameters for disease traits using SNP data. In this review, we summarize the two early papers and put them into context. We show recent extensions of the theory for ascertained case-control data and review recent applications in human genetics. © 2015 Blackwell Verlag GmbH.

Shared responsibility payment for not maintaining minimum essential coverage. Final regulations.

PubMed

2013-08-30

This document contains final regulations on the requirement to maintain minimum essential coverage enacted by the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010, as amended by the TRICARE Affirmation Act and Public Law 111-173. These final regulations provide guidance to individual taxpayers on the liability under section 5000A of the Internal Revenue Code for the shared responsibility payment for not maintaining minimum essential coverage and largely finalize the rules in the notice of proposed rulemaking published in the Federal Register on February 1, 2013.

Analysis of the Interactions between Treaties

DTIC Science & Technology

1992-04-01

PROVISIONS Assist ana protect against chemical weapons UIVERSALITY Research, share/exchange chemi- cals, equipment, information rela. Not applicable ting...liability in the event of injury to a Soviet inspector. U.S. escorts maintain the right to prevent Soviet inspectors from undertaking life ...updated continually through notifications for the life of the Treaty and in total at periodic intervals. The START Treaty requires a myriad of

Family conflict interacts with genetic liability in predicting childhood and adolescent depression.

PubMed

Rice, Frances; Harold, Gordon T; Shelton, Katherine H; Thapar, Anita

2006-07-01

To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms increases as levels of family conflict increase. A longitudinal twin design was used. Children ages 5 to 16 were reassessed approximately 3 years later to test whether the influence of family conflict in predicting depressive symptoms varied according to genetic liability. The conflict subscale of the Family Environment Scale was used to assess family conflict and the Mood and Feelings Questionnaire was used to assess depressive symptoms. The response rate to the questionnaire at time 1 was 73% and 65% at time 2. Controlling for initial symptoms levels (i.e., internalizing at time 1), primary analyses were conducted using ordinary least-squares multiple regression. Structural equation models, using raw score maximum likelihood estimation, were also fit to the data for the purpose of model fit comparison. Results suggested significant gene-environment interaction specifically with depressive symptoms and family conflict. Genetic factors were of greater importance in the etiology of depressive symptoms where levels of family conflict were high. The effects of family conflict on depressive symptoms were greater in children and adolescents at genetic risk of depression. The present results suggest that children with a family history of depression may be at an increased risk of developing depressive symptoms in response to family conflict. Intervention programs that incorporate one or more family systems may be of benefit in alleviating the adverse effect of negative family factors on children.

Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study.

PubMed

Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J

2014-08-01

The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

Preimplantation genetic diagnosis: a systematic review of litigation in the face of new technology.

PubMed

Amagwula, Tochi; Chang, Peter L; Hossain, Amjad; Tyner, Joey; Rivers, Aimée L; Phelps, John Y

2012-11-01

To study legal cases against IVF facilities pertaining to preimplantation genetic diagnosis (PGD) misdiagnosis. Systematic case law review. University medical center using US legal databases. The IVF recipients using PGD services. Lawsuits pertaining to PGD against IVF facilities. Lawsuits, court rulings, damage awards, and settlements pertaining to PGD after the birth of a child with a genetic defect. Causes of action pertaining to PGD arise from negligence in performing the procedure as well as failure to properly inform patients of key information, such as inherent errors associated with the PGD process, a facility's minimal experience in performing PGD, and the option of obtaining PGD. Courts have sympathized with the financial burden involved in caring for children with disabilities. Monetary damage awards are based on the costs of caring for children with debilitating defects, including lifetime medical and custodial care. Facilities offering PGD services expose themselves to a new realm of liability in which damage awards can easily exceed the limits of a facility's insurance policy. Competent laboratory personnel and proper informed consent--with particular care to inform patients of the inherent inaccuracies of PGD--are crucial in helping deter liability. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Lung cancer treatment costs, including patient responsibility, by disease stage and treatment modality, 1992 to 2003.

PubMed

Cipriano, Lauren E; Romanus, Dorothy; Earle, Craig C; Neville, Bridget A; Halpern, Elkan F; Gazelle, G Scott; McMahon, Pamela M

2011-01-01

The objective of this analysis was to estimate costs for lung cancer care and evaluate trends in the share of treatment costs that are the responsibility of Medicare beneficiaries. The Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1991-2003 for 60,231 patients with lung cancer were used to estimate monthly and patient-liability costs for clinical phases of lung cancer (prediagnosis, staging, initial, continuing, and terminal), stratified by treatment, stage, and non-small- versus small-cell lung cancer. Lung cancer-attributable costs were estimated by subtracting each patient's own prediagnosis costs. Costs were estimated as the sum of Medicare reimbursements (payments from Medicare to the service provider), co-insurance reimbursements, and patient-liability costs (deductibles and "co-payments" that are the patient's responsibility). Costs and patient-liability costs were fit with regression models to compare trends by calendar year, adjusting for age at diagnosis. The monthly treatment costs for a 72-year-old patient, diagnosed with lung cancer in 2000, in the first 6 months ranged from $2687 (no active treatment) to $9360 (chemo-radiotherapy); costs varied by stage at diagnosis and histologic type. Patient liability represented up to 21.6% of care costs and increased over the period 1992-2003 for most stage and treatment categories, even when care costs decreased or remained unchanged. The greatest monthly patient liability was incurred by chemo-radiotherapy patients, which ranged from $1617 to $2004 per month across cancer stages. Costs for lung cancer care are substantial, and Medicare is paying a smaller proportion of the total cost over time. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Observation Status, Poverty, and High Financial Liability Among Medicare Beneficiaries.

PubMed

Goldstein, Jennifer N; Zhang, Zugui; Schwartz, J Sanford; Hicks, LeRoi S

2018-01-01

Medicare beneficiaries hospitalized under observation status are subject to cost-sharing with no spending limit under Medicare Part B. Because low-income status is associated with increased hospital use, there is concern that such beneficiaries may be at increased risk for high use and out-of-pocket costs related to observation care. Our objective was to determine whether low-income Medicare beneficiaries are at risk for high use and high financial liability for observation care compared with higher-income beneficiaries. We performed a retrospective, observational analysis of Medicare Part B claims and US Census Bureau data from 2013. Medicare beneficiaries with Part A and B coverage for the full calendar year, with 1 or more observation stay(s), were included in the study. Beneficiaries were divided into quartiles representing poverty level. The associations between poverty quartile and high use of observation care and between poverty quartile and high financial liability for observation care were evaluated. After multivariate adjustment, the risk of high use was higher for beneficiaries in the poor (Quartile 3) and poorest (Quartile 4) quartiles compared with those in the wealthiest quartile (Quartile 1) (adjusted odds ratio [AOR], 1.21; 95% confidence interval [CI], 1.13-1.31; AOR, 1.24; 95% CI, 1.16-1.33). The risk of high financial liability was higher in every poverty quartile compared with the wealthiest and peaked in Quartile 3, which represented the poor but not the poorest beneficiaries (AOR, 1.17; 95% CI, 1.10-1.24). Poverty predicts high use of observation care. The poor or near poor may be at highest risk for high liability. Copyright © 2018 Elsevier Inc. All rights reserved.

Peer Deviance, Parental Divorce, and Genetic Risk in the Prediction of Drug Abuse in a Nationwide Swedish Sample

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-01-01

IMPORTANCE Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). OBJECTIVES To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. DESIGN, SETTING, AND PARTICIPANTS Studies of future DA registration in 1 401 698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. MAIN OUTCOMES AND MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. CONCLUSIONS AND RELEVANCE With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors. PMID:24576925

Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse in a nationwide Swedish sample: evidence of environment-environment and gene-environment interaction.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-04-01

Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. Studies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. Drug abuse recorded in medical, legal, or pharmacy registry records. Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors.

T198. A SCHIZOPHRENIA-LIKE BIRTH SEASONALITY AMONG MATHEMATICIANS AND AN OPPOSITE SEASONALITY AMONG BIOLOGISTS: MORE EVIDENCE IMPLICATING BIMODAL RHYTHMS OF GENERAL BIRTHS

PubMed Central

Marzullo, Giovanni

2018-01-01

Abstract Background Based on early-20th century births, a pre-electric illumination time of comparatively normal human exposure to sunlight, studies of schizophrenia (SCZ) found a birth seasonality with two opposite effects: a SCZ-liability peak among subjects born around late-February and an equally significant SCZ-resistance peak among those born six months later, around late-August. We previously investigated this rhythm in connection with a sunlight-dependent bimodal rhythm of general births that, prior to the full advent of electric lighting (but not later), occurred ubiquitously in non-equatorial parts of the world. We found that the SCZ-liability peak coincided with a first, Feb-Mar peak of general-population births (the GP1) while the SCZ-resistance peak coincided with a second, Aug-Sep peak of those births (the GP2). Moreover, in a study of hand and visual-field preferences among professional baseball players, we found the SCZ-liability, GP1-coincident seasonality among players with preferences denoting cerebral asymmetry “deficits” (CADs) and the SCZ-resistance, GP2-coincident seasonality among those with preferences denoting cerebral asymmetry “excesses.” Also, in a study suggested by associations of CADs with artistic abilities, we found the SCZ-liability, GP1-coincident seasonality among groups representing visual, performing and literary art “creators” (VPL-Artists) and the SCZ-resistance, GP2-coincident seasonality among groups representing art critics, historians, curators and other art “observers” (Para-Artists). Together, these findings suggested, as one possibility (but see later), that the SCZ-liability, CAD effects and artistic abilities could all three represent traits genetically or otherwise selected into the GP1 excess population of newborns and out of the GP2 population. The present study of “scientists” was initially aimed at the purported arts/science antithesis. Methods Birth seasonalities were examined among early-20th century born American scientists and among yet earlier European biologists and mathematicians. Results A group representing 1,925 American scientists showed the SCZ-resistance, GP2-coincident seasonality. However, this effect proved to be mostly due to biologists because biochemists, chemists, and physicists showed gradually less seasonality while mathematicians suggested an altogether artist-like, GP1-coincident seasonality. This intimation of a biologist-mathematician antithesis was pursued with an investigation of most major figures in the history of the two sciences from the 15th to the early-20th century. The two groups, numbering 576 mathematicians and 787 biologists, shared the same mean decade of birth, the 1780s, and essentially the same geographic origin in Western Europe. The mathematicians showed a very significant SCZ liability-like, GP1-coincident seasonality while the biologists showed an even more significant SCZ resistance-like, GP2-coincident seasonality. The latter effect was particularly strong among naturalists, anatomists and other groups representing biological “observationalism” as opposed to “experimentalism.” Discussion The findings are discussed in light of a) new evidence that the annual photoperiod is indeed alone responsible for both peaks of general births, with the GP1 and the GP2 being caused by maternal periconceptional exposure to, respectively, the summer-solstice sunlight maximum and the winter-solstice minimum, and b) an approach/withdrawal theory of lateralization of basic emotions where the left cerebral cortex would handle external stimuli eliciting complacent emotions towards external realities while the right cortex would handle internal stimuli eliciting disdain for those realities.

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

PubMed

Sampson, Joshua N; Wheeler, William A; Yeager, Meredith; Panagiotou, Orestis; Wang, Zhaoming; Berndt, Sonja I; Lan, Qing; Abnet, Christian C; Amundadottir, Laufey T; Figueroa, Jonine D; Landi, Maria Teresa; Mirabello, Lisa; Savage, Sharon A; Taylor, Philip R; De Vivo, Immaculata; McGlynn, Katherine A; Purdue, Mark P; Rajaraman, Preetha; Adami, Hans-Olov; Ahlbom, Anders; Albanes, Demetrius; Amary, Maria Fernanda; An, She-Juan; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L; Angelucci, Emanuele; Ansell, Stephen M; Arici, Cecilia; Armstrong, Bruce K; Arslan, Alan A; Austin, Melissa A; Baris, Dalsu; Barkauskas, Donald A; Bassig, Bryan A; Becker, Nikolaus; Benavente, Yolanda; Benhamou, Simone; Berg, Christine; Van Den Berg, David; Bernstein, Leslie; Bertrand, Kimberly A; Birmann, Brenda M; Black, Amanda; Boeing, Heiner; Boffetta, Paolo; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Brinton, Louise; Brooks-Wilson, Angela R; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chan, John K C; Chang, Ellen T; Chang, Gee-Chen; Chang, I-Shou; Chang, Jiang; Chang-Claude, Jenny; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chu; Chen, Chung-Hsing; Chen, Constance; Chen, Hongyan; Chen, Kexin; Chen, Kuan-Yu; Chen, Kun-Chieh; Chen, Ying; Chen, Ying-Hsiang; Chen, Yi-Song; Chen, Yuh-Min; Chien, Li-Hsin; Chirlaque, María-Dolores; Choi, Jin Eun; Choi, Yi Young; Chow, Wong-Ho; Chung, Charles C; Clavel, Jacqueline; Clavel-Chapelon, Françoise; Cocco, Pierluigi; Colt, Joanne S; Comperat, Eva; Conde, Lucia; Connors, Joseph M; Conti, David; Cortessis, Victoria K; Cotterchio, Michelle; Cozen, Wendy; Crouch, Simon; Crous-Bou, Marta; Cussenot, Olivier; Davis, Faith G; Ding, Ti; Diver, W Ryan; Dorronsoro, Miren; Dossus, Laure; Duell, Eric J; Ennas, Maria Grazia; Erickson, Ralph L; Feychting, Maria; Flanagan, Adrienne M; Foretova, Lenka; Fraumeni, Joseph F; Freedman, Neal D; Beane Freeman, Laura E; Fuchs, Charles; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M; Garcia-Closas, Montserrat; García-Closas, Reina; Gascoyne, Randy D; Gastier-Foster, Julie; Gaudet, Mia M; Gaziano, J Michael; Giffen, Carol; Giles, Graham G; Giovannucci, Edward; Glimelius, Bengt; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M; Gorlick, Richard; Gross, Myron; Grubb, Robert; Gu, Jian; Guan, Peng; Gunter, Marc; Guo, Huan; Habermann, Thomas M; Haiman, Christopher A; Halai, Dina; Hallmans, Goran; Hassan, Manal; Hattinger, Claudia; He, Qincheng; He, Xingzhou; Helzlsouer, Kathy; Henderson, Brian; Henriksson, Roger; Hjalgrim, Henrik; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holford, Theodore R; Holly, Elizabeth A; Hong, Yun-Chul; Hoover, Robert N; Horn-Ross, Pamela L; Hosain, G M Monawar; Hosgood, H Dean; Hsiao, Chin-Fu; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Huerta, Jose-Maria; Hung, Jen-Yu; Hutchinson, Amy; Inskip, Peter D; Jackson, Rebecca D; Jacobs, Eric J; Jenab, Mazda; Jeon, Hyo-Sung; Ji, Bu-Tian; Jin, Guangfu; Jin, Li; Johansen, Christoffer; Johnson, Alison; Jung, Yoo Jin; Kaaks, Rudolph; Kamineni, Aruna; Kane, Eleanor; Kang, Chang Hyun; Karagas, Margaret R; Kelly, Rachel S; Khaw, Kay-Tee; Kim, Christopher; Kim, Hee Nam; Kim, Jin Hee; Kim, Jun Suk; Kim, Yeul Hong; Kim, Young Tae; Kim, Young-Chul; Kitahara, Cari M; Klein, Alison P; Klein, Robert J; Kogevinas, Manolis; Kohno, Takashi; Kolonel, Laurence N; Kooperberg, Charles; Kricker, Anne; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C; Kweon, Sun-Seog; LaCroix, Andrea; Lawrence, Charles; Lecanda, Fernando; Lee, Victor Ho Fun; Li, Donghui; Li, Haixin; Li, Jihua; Li, Yao-Jen; Li, Yuqing; Liao, Linda M; Liebow, Mark; Lightfoot, Tracy; Lim, Wei-Yen; Lin, Chien-Chung; Lin, Dongxin; Lindstrom, Sara; Linet, Martha S; Link, Brian K; Liu, Chenwei; Liu, Jianjun; Liu, Li; Ljungberg, Börje; Lloreta, Josep; Di Lollo, Simonetta; Lu, Daru; Lund, Eiluv; Malats, Nuria; Mannisto, Satu; Le Marchand, Loic; Marina, Neyssa; Masala, Giovanna; Mastrangelo, Giuseppe; Matsuo, Keitaro; Maynadie, Marc; McKay, James; McKean-Cowdin, Roberta; Melbye, Mads; Melin, Beatrice S; Michaud, Dominique S; Mitsudomi, Tetsuya; Monnereau, Alain; Montalvan, Rebecca; Moore, Lee E; Mortensen, Lotte Maxild; Nieters, Alexandra; North, Kari E; Novak, Anne J; Oberg, Ann L; Offit, Kenneth; Oh, In-Jae; Olson, Sara H; Palli, Domenico; Pao, William; Park, In Kyu; Park, Jae Yong; Park, Kyong Hwa; Patiño-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H M; Perng, Reury-Perng; Peters, Ulrike; Petersen, Gloria M; Picci, Piero; Pike, Malcolm C; Porru, Stefano; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Qian, Biyun; Qiao, You-Lin; Rais, Marco; Riboli, Elio; Riby, Jacques; Risch, Harvey A; Rizzato, Cosmeri; Rodabough, Rebecca; Roman, Eve; Roupret, Morgan; Ruder, Avima M; Sanjose, Silvia de; Scelo, Ghislaine; Schned, Alan; Schumacher, Fredrick; Schwartz, Kendra; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D; Setiawan, Veronica Wendy; Severi, Gianluca; Severson, Richard K; Shanafelt, Tait D; Shen, Hongbing; Shen, Wei; Shin, Min-Ho; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesúmaga, Luis; Sihoe, Alan Dart Loon; Skibola, Christine F; Smith, Alex; Smith, Martyn T; Southey, Melissa C; Spinelli, John J; Staines, Anthony; Stampfer, Meir; Stern, Marianna C; Stevens, Victoria L; Stolzenberg-Solomon, Rachael S; Su, Jian; Su, Wu-Chou; Sund, Malin; Sung, Jae Sook; Sung, Sook Whan; Tan, Wen; Tang, Wei; Tardón, Adonina; Thomas, David; Thompson, Carrie A; Tinker, Lesley F; Tirabosco, Roberto; Tjønneland, Anne; Travis, Ruth C; Trichopoulos, Dimitrios; Tsai, Fang-Yu; Tsai, Ying-Huang; Tucker, Margaret; Turner, Jenny; Vajdic, Claire M; Vermeulen, Roel C H; Villano, Danylo J; Vineis, Paolo; Virtamo, Jarmo; Visvanathan, Kala; Wactawski-Wende, Jean; Wang, Chaoyu; Wang, Chih-Liang; Wang, Jiu-Cun; Wang, Junwen; Wei, Fusheng; Weiderpass, Elisabete; Weiner, George J; Weinstein, Stephanie; Wentzensen, Nicolas; White, Emily; Witzig, Thomas E; Wolpin, Brian M; Wong, Maria Pik; Wu, Chen; Wu, Guoping; Wu, Junjie; Wu, Tangchun; Wu, Wei; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S; Xiang, Yong-Bing; Xu, Jun; Xu, Ping; Yang, Pan-Chyr; Yang, Tsung-Ying; Ye, Yuanqing; Yin, Zhihua; Yokota, Jun; Yoon, Ho-Il; Yu, Chong-Jen; Yu, Herbert; Yu, Kai; Yuan, Jian-Min; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Xu-Chao; Zhang, Yawei; Zhao, Xueying; Zhao, Zhenhong; Zheng, Hong; Zheng, Tongzhang; Zheng, Wei; Zhou, Baosen; Zhu, Meng; Zucca, Mariagrazia; Boca, Simina M; Cerhan, James R; Ferri, Giovanni M; Hartge, Patricia; Hsiung, Chao Agnes; Magnani, Corrado; Miligi, Lucia; Morton, Lindsay M; Smedby, Karin E; Teras, Lauren R; Vijai, Joseph; Wang, Sophia S; Brennan, Paul; Caporaso, Neil E; Hunter, David J; Kraft, Peter; Rothman, Nathaniel; Silverman, Debra T; Slager, Susan L; Chanock, Stephen J; Chatterjee, Nilanjan

2015-12-01

Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Genetic liability, environment, and the development of fussiness in toddlers: the roles of maternal depression and parental responsiveness.

PubMed

Natsuaki, Misaki N; Ge, Xiaojia; Leve, Leslie D; Neiderhiser, Jenae M; Shaw, Daniel S; Conger, Rand D; Scaramella, Laura V; Reid, John B; Reiss, David

2010-09-01

Using a longitudinal, prospective adoption design, the authors of this study examined the effects of the environment (adoptive parents' depressive symptoms and responsiveness) and genetic liability of maternal depression (inferred by birth mothers' major depressive disorder [MDD]) on the development of fussiness in adopted children between 9 and 18 months old. The sample included 281 families linked through adoption, with each family including 4 individuals (i.e., adopted child, birth mother, adoptive father and mother). Results showed that adoptive mothers' depressive symptoms when their child was 9 months old were positively associated with child fussiness at 18 months. A significant interaction between birth mothers' MDD and adoptive mothers' responsiveness indicated that children of birth mothers with MDD showed higher levels of fussiness at 18 months when adoptive mothers had been less responsive to the children at 9 months. However, in the context of high levels of adoptive mothers' responsiveness, children of birth mothers with MDD did not show elevated fussiness at 18 months. Findings are discussed in terms of gene-environment interactions in the intergenerational risk transmission of depression.

Neurocognitive performance as an endophenotype for bipolar disorder.

PubMed

Raust, Aurelie; Daban, Claire; Cochet, Barbara; Henry, Chantal; Bellivier, Frank; Scott, Jan

2014-01-01

Identification of the underlying liability to develop bipolar disorders (BD) is hindered by the genetic complexity and phenotypic heterogeneity of the disease. The use of endophenotypes has been acknowledged as a promising approach that may detect the hidden manifestations of a genetic liability for an illness. One of the most commonly proposed endophenotypes in BD is neurocognitive performance. We identified and examined previously published review articles that had any data pertaining to endophenotypes in BD and combined this with an extensive review of studies of cognitive deficits in BD from 2000 onwards. Using criteria for a valid endophenotype, we identifed that the domains of executive functioning and verbal memory are the most promising candidate endophenotypes for BD. However, they do not meet the criteria for specificity as similar deficits present in schizophrenia and/or severe or psychotic major depressions. Further research is needed as the findings regarding endophenotypes show between-study heterogeneity. In the future, examination of quantitative traits may offer a more promising approach to the study of endophenotypes rather than solely focusing on diagnostic categories.

Genetic vulnerability interacts with parenting and early care education to predict increasing externalizing behavior.

PubMed

Lipscomb, Shannon T; Laurent, Heidemarie; Neiderhiser, Jenae M; Shaw, Daniel S; Natsuaki, Misaki N; Reiss, David; Leve, Leslie D

2014-01-01

The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children.

Genetic vulnerability interacts with parenting and early care education to predict increasing externalizing behavior

PubMed Central

Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.

2014-01-01

The current study examined interactions among genetic influences and children’s early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children. PMID:25067867

Hereditary neuropathy with liability to pressure palsies presenting with sciatic neuropathy.

PubMed

Topakian, Raffi; Wimmer, Sibylle; Pischinger, Barbara; Pichler, Robert

2014-10-17

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing. 2014 BMJ Publishing Group Ltd.

Liability of newness: assessing couple social support when starting a new business venture.

PubMed

Danes, Sharon M; Craft, Shonda M; Jang, Juyoung; Lee, Jinhee

2013-10-01

Study purpose was to investigate adapted social support instruments of nurturance and affiliation with male and female entrepreneurs and spouses starting a new business. Family Fundamental Interpersonal Relationship Orientation theory was the theoretical grounding. Business structure differed by entrepreneur gender in both direct and indirect spousal involvement. Both couple types were highly connected with their firms having high nurturance and affiliation scores. When couple discrepancies were compared, more male entrepreneur couples had shared meaning on business-oriented nurturance questions compared with female entrepreneur couples. The opposite was true for shared meaning on relationship-oriented nurturance. For all affiliation questions, more male entrepreneur couples had shared meaning than did female entrepreneur couples. Clinical applications of resulting instruments are discussed. © 2013 American Association for Marriage and Family Therapy.

Quantitative genetic properties of four measures of deformity in yellowtail kingfish Seriola lalandi Valenciennes, 1833.

PubMed

Nguyen, N H; Whatmore, P; Miller, A; Knibb, W

2016-02-01

The main aim of this study was to estimate the heritability for four measures of deformity and their genetic associations with growth (body weight and length), carcass (fillet weight and yield) and flesh-quality (fillet fat content) traits in yellowtail kingfish Seriola lalandi. The observed major deformities included lower jaw, nasal erosion, deformed operculum and skinny fish on 480 individuals from 22 families at Clean Seas Tuna Ltd. They were typically recorded as binary traits (presence or absence) and were analysed separately by both threshold generalized models and standard animal mixed models. Consistency of the models was evaluated by calculating simple Pearson correlation of breeding values of full-sib families for jaw deformity. Genetic and phenotypic correlations among traits were estimated using a multitrait linear mixed model in ASReml. Both threshold and linear mixed model analysis showed that there is additive genetic variation in the four measures of deformity, with the estimates of heritability obtained from the former (threshold) models on liability scale ranging from 0.14 to 0.66 (SE 0.32-0.56) and from the latter (linear animal and sire) models on original (observed) scale, 0.01-0.23 (SE 0.03-0.16). When the estimates on the underlying liability were transformed to the observed scale (0, 1), they were generally consistent between threshold and linear mixed models. Phenotypic correlations among deformity traits were weak (close to zero). The genetic correlations among deformity traits were not significantly different from zero. Body weight and fillet carcass showed significant positive genetic correlations with jaw deformity (0.75 and 0.95, respectively). Genetic correlation between body weight and operculum was negative (-0.51, P < 0.05). The genetic correlations' estimates of body and carcass traits with other deformity were not significant due to their relatively high standard errors. Our results showed that there are prospects for genetic selection to improve deformity in yellowtail kingfish and that measures of deformity should be included in the recording scheme, breeding objectives and selection index in practical selective breeding programmes due to the antagonistic genetic correlations of deformed jaws with body and carcass performance. © 2015 John Wiley & Sons Ltd.

Identification of genetic loci shared between schizophrenia and the Big Five personality traits.

PubMed

Smeland, Olav B; Wang, Yunpeng; Lo, Min-Tzu; Li, Wen; Frei, Oleksandr; Witoelar, Aree; Tesli, Martin; Hinds, David A; Tung, Joyce Y; Djurovic, Srdjan; Chen, Chi-Hua; Dale, Anders M; Andreassen, Ole A

2017-05-22

Schizophrenia is associated with differences in personality traits, and recent studies suggest that personality traits and schizophrenia share a genetic basis. Here we aimed to identify specific genetic loci shared between schizophrenia and the Big Five personality traits using a Bayesian statistical framework. Using summary statistics from genome-wide association studies (GWAS) on personality traits in the 23andMe cohort (n = 59,225) and schizophrenia in the Psychiatric Genomics Consortium cohort (n = 82,315), we evaluated overlap in common genetic variants. The Big Five personality traits neuroticism, extraversion, openness, agreeableness and conscientiousness were measured using a web implementation of the Big Five Inventory. Applying the conditional false discovery rate approach, we increased discovery of genetic loci and identified two loci shared between neuroticism and schizophrenia and six loci shared between openness and schizophrenia. The study provides new insights into the relationship between personality traits and schizophrenia by highlighting genetic loci involved in their common genetic etiology.

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction

PubMed Central

Cadoni, Cristina

2016-01-01

Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40–60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore, the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis on differences in mesolimbic dopamine (DA) transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neuron functionality. Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigation, results from the reviewed studies might open new vistas in understanding aberrant deviations in reward and motivational functions. PMID:26903787

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction.

PubMed

Cadoni, Cristina

2016-01-01

Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore, the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis on differences in mesolimbic dopamine (DA) transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neuron functionality. Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigation, results from the reviewed studies might open new vistas in understanding aberrant deviations in reward and motivational functions.

Pros and cons of the ambulatory surgery center joint venture.

PubMed

Giannini, Deborah

2008-01-01

If a physician group has determined that it has a realistic patient base to establish an ambulatory surgery center, it may be beneficial to consider a partner to share the costs and risks of this new joint venture. Joint ventures can be a benefit or liability in the establishment of an ambulatory surgery center. This article discusses the advantages and disadvantages of a hospital physician-group joint venture.

Familial liability to psychosis is a risk factor for multimorbidity in people with psychotic disorders and their unaffected siblings.

PubMed

Islam, M A; Khan, M F H; Quee, P J; Snieder, H; van den Heuvel, E R; Bruggeman, R; Alizadeh, B Z

2017-09-01

Multimorbidity may impose an overwhelming burden on patients with psychosis and is affected by gender and age. Our aim is to study the independent role of familial liability to psychosis as a risk factor for multimorbidity. We performed the study within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic patients, 994 unaffected siblings and 566 controls on the prevalence of 125 lifetime diseases, and 19 self-reported somatic complaints. Multimorbidity was defined as the presence of two or more complaints/diseases in the same individual. Generalized linear mixed model (GLMM) were used to investigate the effects of gender, age (adolescent, young, older) and familial liability (patients, siblings, controls) and their interactions on multimorbidity. Familial liability had a significant effect on multimorbidity of either complaints or diseases. Patients had a higher prevalence of multimorbidity of complaints compared to siblings (OR 2.20, 95% CI 1.79-2.69, P<0.001) and to controls (3.05, 2.35-3.96, P<0.001). In physical health multimorbidity, patients (OR 1.36, 95% CI 1.05-1.75, P=0.018), but not siblings, had significantly higher prevalence than controls. Similar finding were observed for multimorbidity of lifetime diseases, including psychiatric diseases. Significant results were observed for complaints and disease multimorbidity across gender and age groups. Multimorbidity is a common burden, significantly more prevalent in patients and their unaffected siblings. Familial liability to psychosis showed an independent effect on multimorbidity; gender and age are also important factors determining multimorbidity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Can I be sued for that? Liability risk and the disclosure of clinically significant genetic research findings

PubMed Central

McGuire, Amy L.; Knoppers, Bartha Maria; Zawati, Ma’n H.; Clayton, Ellen Wright

2014-01-01

Genomic researchers increasingly are faced with difficult decisions about whether, under what circumstances, and how to return research results and significant incidental findings to study participants. Many have argued that there is an ethical—maybe even a legal—obligation to disclose significant findings under some circumstances. At the international level, over the last decade there has begun to emerge a clear legal obligation to return significant findings discovered during the course of research. However, there is no explicit legal duty to disclose in the United States. This creates legal uncertainty that may lead to unmanaged variation in practice and poor quality care. This article discusses liability risks associated with the disclosure of significant research findings for investigators in the United States. PMID:24676095

Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia.

PubMed

Lee, Tae Young; Kim, Minah; Kim, Sung Nyun; Kwon, Jun Soo

2017-01-01

The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influence of genetic vulnerability and environmental stress even after the peak age of onset of schizophrenia. Therefore, individuals with genetic liability of schizophrenia may require a more intensive intervention than recommended by the staging model based on current clinical status.

Shared genetic contributions of fruit and vegetable consumption with BMI in families 20 y after sharing a household.

PubMed

Martin, Lisa J; Lee, Seung-Yeon; Couch, Sarah C; Morrison, John; Woo, Jessica G

2011-10-01

Obesity has a strong genetic basis, but the identification of genetic variants has not resulted in improved clinical care. However, phenotypes that influence weight, such as diet, may have shared underpinnings with obesity. Interestingly, diet also has a genetic basis. Thus, we hypothesized that the genetic underpinnings of diet may partially overlap with the genetics of obesity. Our objective was to determine whether dietary intake and BMI share heritable components in adulthood. We used a cross-sectional cohort of parents and adult offspring (n = 1410) from the Princeton Follow-up Study. Participants completed Block food-frequency questionnaires 15-27 y after sharing a household. Heritability of dietary intakes was estimated by using variance components analysis. Bivariate genetic analyses were used to estimate the shared effects between BMI and heritable dietary intakes. Fruit, vegetable, and protein consumption exhibited moderate heritability [(mean ± SE) 0.26 ± 0.06, 0.32 ± 0.06, and 0.21 ± 0.06, respectively; P < 0.001], but other dietary intakes were modest (h(2) < 0.2). Only fruit and vegetable consumption exhibited genetic correlations with BMI (ρ(g) = -0.28 ± 0.13 and -0.30 ± 0.13, respectively; P < 0.05). Phenotypic correlations with BMI were not significant. We showed that fruit, vegetable, and protein intakes are moderately heritable and that fruit and vegetable consumption shares underlying genetic effects with BMI in adulthood, which suggests that individuals genetically predisposed to low fruit and vegetable consumption may be predisposed to higher BMI. Thus, obese individuals who have low fruit and vegetable consumption may require targeted interventions that go beyond low-calorie, plant-based programs for weight management.

A common variant in DRD3 receptor is associated with autism spectrum disorder.

PubMed

de Krom, Mariken; Staal, Wouter G; Ophoff, Roel A; Hendriks, Judith; Buitelaar, Jan; Franke, Barbara; de Jonge, Maretha V; Bolton, Patrick; Collier, David; Curran, Sarah; van Engeland, Herman; van Ree, Jan M

2009-04-01

The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study. 1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample. No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162). The DRD3 gene is related to stereotyped behavior, liability to side effects of antipsychotic medication, and movement disorders and may therefore have important clinical implications for ASD.

Genetic pleiotropy explains associations between musical auditory discrimination and intelligence.

PubMed

Mosing, Miriam A; Pedersen, Nancy L; Madison, Guy; Ullén, Fredrik

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions.

Genetic Pleiotropy Explains Associations between Musical Auditory Discrimination and Intelligence

PubMed Central

Mosing, Miriam A.; Pedersen, Nancy L.; Madison, Guy; Ullén, Fredrik

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions. PMID:25419664

Genetic and environmental factors affecting birth size variation: a pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts.

PubMed

Yokoyama, Yoshie; Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo; Fagnani, Corrado; Stazi, Maria A; Brescianini, Sonia; Ji, Fuling; Ning, Feng; Pang, Zengchang; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Rebato, Esther; Hopper, John L; Cutler, Tessa L; Saudino, Kimberly J; Nelson, Tracy L; Whitfield, Keith E; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Llewellyn, Clare H; Fisher, Abigail; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Bartels, Meike; van Beijsterveldt, Catharina E M; Willemsen, Gonneke; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Craig, Jeffrey M; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Haworth, Claire M A; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Rasmussen, Finn; Tynelius, Per; Tarnoki, Adam D; Tarnoki, David L; Ooki, Syuichi; Rose, Richard J; Pietiläinen, Kirsi H; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko; Silventoinen, Karri

2018-05-19

The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.

Examining the etiological associations among higher-order temperament dimensions

PubMed Central

Allan, Nicholas P.; Mikolajewski, Amy J.; Lonigan, Christopher J.; Hart, Sara A.; Taylor, Jeanette

2014-01-01

A multivariate independent pathway model was used to examine the shared and unique genetic and environmental influences of Positive Affect (PA), Negative Affect (NA), and effortful control (EC) in a sample of 686 twin pairs (M age = 10.07, SD = 1.74). There were common genetic influences and nonshared environmental influences shared across all three temperament dimensions and shared environmental influences in common to NA and EC. There were also significant independent genetic influences unique to PA and NA and significant independent shared environmental influences unique to PA. This study demonstrates that there are genetic and environmental influences that affect the covariance among temperament dimensions as well as unique genetic and environmental influences that influence the dimensions independently. PMID:24729641

Brief Report: Do the Nature of Communication Impairments in Autism Spectrum Disorders Relate to the Broader Autism Phenotype in Parents?

ERIC Educational Resources Information Center

Taylor, Lauren J.; Maybery, Murray T.; Wray, John; Ravine, David; Hunt, Anna; Whitehouse, Andrew J. O.

2013-01-01

Extensive empirical evidence indicates that the lesser variant of Autism Spectrum Disorders (ASD) involves a communication impairment that is similar to, but milder than, the deficit in clinical ASD. This research explored the relationship between the broader autism phenotype (BAP) among parents, an index of genetic liability for ASD, and proband…

Peripheral neuropathy in patients with HIV infection: consider dual pathology.

PubMed

Miller, R F; Bunting, S; Sadiq, S T; Manji, H

2002-12-01

Two HIV infected patients presented with peripheral neuropathy, in one patient this was originally ascribed to HIV associated mononeuritis multiplex and in the other to stavudine. Investigations confirmed these diagnoses and in both cases genetic analysis identified a second hereditary aetiology: in the first patient hereditary neuropathy with liability to pressure palsies and in the second hereditary motor and sensory neuropathy.

Neuroscience of resilience and vulnerability for addiction medicine: From genes to behavior.

PubMed

Morrow, Jonathan D; Flagel, Shelly B

2016-01-01

Addiction is a complex behavioral disorder arising from roughly equal contributions of genetic and environmental factors. Behavioral traits such as novelty-seeking, impulsivity, and cue-reactivity have been associated with vulnerability to addiction. These traits, at least in part, arise from individual variation in functional neural systems, such as increased striatal dopaminergic activity and decreased prefrontal cortical control over subcortical emotional and motivational responses. With a few exceptions, genetic studies have largely failed to consistently identify specific alleles that affect addiction liability. This may be due to the multifactorial nature of addiction, with different genes becoming more significant in certain environments or in certain subsets of the population. Epigenetic mechanisms may also be an important source of risk. Adolescence is a particularly critical time period in the development of addiction, and environmental factors at this stage of life can have a large influence on whether inherited risk factors are actually translated into addictive behaviors. Knowledge of how individual differences affect addiction liability at the level of genes, neural systems, behavioral traits, and sociodevelopmental trajectories can help to inform and improve clinical practice. © 2016 Elsevier B.V. All rights reserved.

Evidence of a Prominent Genetic Basis for Associations between Psychoneurometric Traits and Common Mental Disorders

PubMed Central

Venables, Noah C.; Hicks, Brian M.; Yancey, James R.; Kramer, Mark D.; Nelson, Lindsay D.; Strickland, Casey M.; Krueger, Robert F.; Iacono, William G.; Patrick, Christopher J.

2016-01-01

Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is first important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N = 454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (.45, .68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically-oriented research on psychopathology. PMID:27671504

Childhood victimization and inflammation in young adulthood: A genetically sensitive cohort study.

PubMed

Baldwin, Jessie R; Arseneault, Louise; Caspi, Avshalom; Fisher, Helen L; Moffitt, Terrie E; Odgers, Candice L; Pariante, Carmine; Ambler, Antony; Dove, Rosamund; Kepa, Agnieszka; Matthews, Timothy; Menard, Anne; Sugden, Karen; Williams, Benjamin; Danese, Andrea

2018-01-01

Childhood victimization is an important risk factor for later immune-related disorders. Previous evidence has demonstrated that childhood victimization is associated with elevated levels of inflammation biomarkers measured decades after exposure. However, it is unclear whether this association is (1) already detectable in young people, (2) different in males and females, and (3) confounded by genetic liability to inflammation. Here we sought to address these questions. Participants were 2232 children followed from birth to age 18years as part of the Environmental Risk (E-Risk) Longitudinal Twin Study. Childhood victimization was measured prospectively from birth to age 12years. Inflammation was measured through C-reactive protein (CRP) levels in dried blood spots at age 18years. Latent genetic liability for high inflammation levels was assessed through a twin-based method. Greater exposure to childhood victimization was associated with higher CRP levels at age 18 (serum-equivalent means were 0.65 in non-victimized Study members, 0.74 in those exposed to one victimization type, and 0.81 in those exposed to poly-victimization; p=0.018). However, this association was driven by a significant association in females (serum-equivalent means were 0.75 in non-victimized females, 0.87 in those exposed to one type of victimization, and 1.19 in those exposed to poly-victimization; p=0.010), while no significant association was observed in males (p=0.19). Victimized females showed elevated CRP levels independent of latent genetic influence, as well as childhood socioeconomic status, and waist-hip ratio and body temperature at the time of CRP assessment. Childhood victimization is associated with elevated CRP levels in young women, independent of latent genetic influences and other key risk factors. These results strengthen causal inference about the effects of childhood victimization on inflammation levels in females by accounting for potential genetic confounding. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Mixed Model Association with Family-Biased Case-Control Ascertainment.

PubMed

Hayeck, Tristan J; Loh, Po-Ru; Pollack, Samuela; Gusev, Alexander; Patterson, Nick; Zaitlen, Noah A; Price, Alkes L

2017-01-05

Mixed models have become the tool of choice for genetic association studies; however, standard mixed model methods may be poorly calibrated or underpowered under family sampling bias and/or case-control ascertainment. Previously, we introduced a liability threshold-based mixed model association statistic (LTMLM) to address case-control ascertainment in unrelated samples. Here, we consider family-biased case-control ascertainment, where case and control subjects are ascertained non-randomly with respect to family relatedness. Previous work has shown that this type of ascertainment can severely bias heritability estimates; we show here that it also impacts mixed model association statistics. We introduce a family-based association statistic (LT-Fam) that is robust to this problem. Similar to LTMLM, LT-Fam is computed from posterior mean liabilities (PML) under a liability threshold model; however, LT-Fam uses published narrow-sense heritability estimates to avoid the problem of biased heritability estimation, enabling correct calibration. In simulations with family-biased case-control ascertainment, LT-Fam was correctly calibrated (average χ 2 = 1.00-1.02 for null SNPs), whereas the Armitage trend test (ATT), standard mixed model association (MLM), and case-control retrospective association test (CARAT) were mis-calibrated (e.g., average χ 2 = 0.50-1.22 for MLM, 0.89-2.65 for CARAT). LT-Fam also attained higher power than other methods in some settings. In 1,259 type 2 diabetes-affected case subjects and 5,765 control subjects from the CARe cohort, downsampled to induce family-biased ascertainment, LT-Fam was correctly calibrated whereas ATT, MLM, and CARAT were again mis-calibrated. Our results highlight the importance of modeling family sampling bias in case-control datasets with related samples. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Testing Models for the Contributions of Genes and Environment to Developmental Change in Adolescent Depression

PubMed Central

Eaves, Lindon J.; Maes, Hermine; Silberg, Judy L.

2015-01-01

We tested two models to identify the genetic and environmental processes underlying longitudinal changes in depression among adolescents. The first assumes that observed changes in covariance structure result from the unfolding of inherent, random individual differences in the overall levels and rates of change in depression over time (random growth curves). The second assumes that observed changes are due to time-specific random effects (innovations) accumulating over time (autoregressive effects). We found little evidence of age-specific genetic effects or persistent genetic innovations. Instead, genetic effects are consistent with a gradual unfolding in the liability to depression and rates of change with increasing age. Likewise, the environment also creates significant individual differences in overall levels of depression and rates of change. However, there are also time-specific environmental experiences that persist with fidelity. The implications of these differing genetic and environmental mechanisms in the etiology of depression are considered. PMID:25894924

Testing Models for the Contributions of Genes and Environment to Developmental Change in Adolescent Depression.

PubMed

Gillespie, Nathan A; Eaves, Lindon J; Maes, Hermine; Silberg, Judy L

2015-07-01

We tested two models to identify the genetic and environmental processes underlying longitudinal changes in depression among adolescents. The first assumes that observed changes in covariance structure result from the unfolding of inherent, random individual differences in the overall levels and rates of change in depression over time (random growth curves). The second assumes that observed changes are due to time-specific random effects (innovations) accumulating over time (autoregressive effects). We found little evidence of age-specific genetic effects or persistent genetic innovations. Instead, genetic effects are consistent with a gradual unfolding in the liability to depression and rates of change with increasing age. Likewise, the environment also creates significant individual differences in overall levels of depression and rates of change. However, there are also time-specific environmental experiences that persist with fidelity. The implications of these differing genetic and environmental mechanisms in the etiology of depression are considered.

Genetics of Nicotine Dependence and Pharmacotherapy

PubMed Central

Lessov-Schlaggar, Christina N.; Pergadia, Michele L.; Khroyan, Taline V.; Swan, Gary E.

2008-01-01

Nicotine dependence is substantially heritable. Several regions across the genome have been implicated in containing genes that confer liability to nicotine dependence and variation in individual genes has been associated with nicotine dependence. Smoking cessation measures are also heritable, and measured genetic variation is associated with nicotine dependence treatment efficacy. Despite significant strides in the understanding of the relative contribution of genetic and environmental factors to nicotine dependence and treatment, emergent challenges necessitate interdisciplinary coordinated effort for effective problem solving. These challenges include refinement of the nicotine dependence phenotype, better understanding of the dynamic interplay between genes and environment in nicotine dependence etiology, application and development of molecular and statistical methodology that can adequately address vast amounts of data, and continuous translational cross-talk. PMID:17888884

Gene-Environment Correlation and Interaction in Peer Effects on Adolescent Alcohol and Tobacco Use

PubMed Central

Harden, K. Paige; Hill, Jennifer E.; Turkheimer, Eric; Emery, Robert E.

2010-01-01

Peer relationships are commonly thought to be critical for adolescent socialization, including the development of negative health behaviors such as alcohol and tobacco use. The interplay between genetic liability and peer influences on the development of adolescent alcohol and tobacco use was examined using a nationally-representative sample of adolescent sibling pairs and their best friends. Genetic factors, some of them related to an adolescent's own substance use and some of them independent of use, were associated with increased exposure to best friends with heavy substance use—a gene-environment correlation. Moreover, adolescents who were genetically liable to substance use were more vulnerable to the adverse influences of their best friends—a gene-environment interaction. PMID:18368474

Intergenerational Transmission of Childhood Conduct Problems

PubMed Central

D’Onofrio, Brian M.; Slutske, Wendy S.; Turkheimer, Eric; Emery, Robert E.; Paige Harden, K.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.

2010-01-01

Context The familial nature of childhood conduct problems has been well documented, but few genetically informed studies have explicitly explored the processes through which parental conduct problems influence an offspring’s behavior problems. Objective To delineate the genetic and environmental processes underlying the intergenerational transmission of childhood conduct problems. Design We used hierarchical linear models to analyze data from a Children of Twins Study, a quasiexperimental design, to explore the extent to which genetic factors common to both generations, unmeasured environmental factors that are shared by twins, or measured characteristics of both parents confound the intergenerational association. Setting Participants were recruited from the community and completed a semistructured diagnostic telephone interview. Participants The research used a high-risk sample of twins, their spouses, and their young adult offspring (n=2554) from 889 twin families in the Australian Twin Registry, but the analyses used sample weights to produce parameter estimates for the community-based volunteer sample of twins. Main Outcome Measure Number of conduct disorder symptoms. Results The magnitude of the intergenerational transmission was significant for all offspring, though it was stronger for males (effect size [Cohen d]=0.21; 95% confidence interval, 0.15–0.17) than females (d=0.09; 95% confidence interval, 0.05–0.14). The use of the Children of Twins design and measured covariates indicated that the intergenerational transmission of conduct problems for male offspring was largely mediated by environmental variables specifically related to parental conduct disorder (d=0.13; 95% confidence interval, 0.02–0.23). In contrast, the intergenerational transmission of conduct problems was not because of environmentally mediated causal processes for female offspring (d=−0.09; 95% confidence interval, −0.20 to 0.03); a common genetic liability accounted for the intergenerational relations. Conclusions The mechanisms underlying the inter-generational transmission of conduct problems depend on the sex of the offspring. The results are consistent with an environmentally mediated causal role of parental conduct problems on behavior problems in males. Common genetic risk, however, confounds the entire inter-generational transmission in female offspring. PMID:17606816

Adventitious Presence of Patented Genetically Modified Organisms on Private Premises: Is Intent Necessary for Actions in Infringement against the Property Owner?

ERIC Educational Resources Information Center

Mgbeoji, Ikechi

2007-01-01

The law of patents has long struggled with the status of intent in determining liability for infringement. This struggle has recently been given a sharper edge by the emergence of biotechnological products with the inherent ability of auto-dispersal and regeneration. The question thus is whether a person on whose backyard a patented genetic…

Nurture Net of Nature: Re-Evaluating the Role of Shared Environments in Academic Achievement and Verbal Intelligence

PubMed Central

Daw, Jonathan; Guo, Guang; Harris, Kathie Mullan

2016-01-01

Prominent authors in the behavioral genetics tradition have long argued that shared environments do not meaningfully shape intelligence and academic achievement. However, we argue that these conclusions are erroneous due to large violations of the additivity assumption underlying behavioral genetics methods – that sources of genetic and shared and nonshared environmental variance are independent and non-interactive. This is compounded in some cases by the theoretical equation of the effective and objective environments, where the former is defined by whether siblings are made more or less similar, and the latter by whether siblings are equally subject to the environmental characteristic in question. Using monozygotic twin fixed effects models, which compare outcomes among genetically identical pairs, we show that many characteristics of objectively shared environments significantly moderate the effects of nonshared environments on adolescent academic achievement and verbal intelligence, violating the additivity assumption of behavioral genetic methods. Importantly, these effects would be categorized as nonshared environmental influences in standard twin models despite their roots in shared environments. These findings should encourage caution among those who claim that the frequently trivial variance attributed to shared environments in behavioral genetic models means that families, schools, and neighborhoods do not meaningfully influence these outcomes. PMID:26004471

Nurture net of nature: Re-evaluating the role of shared environments in academic achievement and verbal intelligence.

PubMed

Daw, Jonathan; Guo, Guang; Harris, Kathie Mullan

2015-07-01

Prominent authors in the behavioral genetics tradition have long argued that shared environments do not meaningfully shape intelligence and academic achievement. However, we argue that these conclusions are erroneous due to large violations of the additivity assumption underlying behavioral genetics methods - that sources of genetic and shared and nonshared environmental variance are independent and non-interactive. This is compounded in some cases by the theoretical equation of the effective and objective environments, where the former is defined by whether siblings are made more or less similar, and the latter by whether siblings are equally subject to the environmental characteristic in question. Using monozygotic twin fixed effects models, which compare outcomes among genetically identical pairs, we show that many characteristics of objectively shared environments significantly moderate the effects of nonshared environments on adolescent academic achievement and verbal intelligence, violating the additivity assumption of behavioral genetic methods. Importantly, these effects would be categorized as nonshared environmental influences in standard twin models despite their roots in shared environments. These findings should encourage caution among those who claim that the frequently trivial variance attributed to shared environments in behavioral genetic models means that families, schools, and neighborhoods do not meaningfully influence these outcomes. Copyright © 2015. Published by Elsevier Inc.

Assessing the evidence for shared genetic risks across psychiatric disorders and traits.

PubMed

Martin, Joanna; Taylor, Mark J; Lichtenstein, Paul

2017-12-04

Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.

PubMed

Ferreira, Manuel A; Vonk, Judith M; Baurecht, Hansjörg; Marenholz, Ingo; Tian, Chao; Hoffman, Joshua D; Helmer, Quinta; Tillander, Annika; Ullemar, Vilhelmina; van Dongen, Jenny; Lu, Yi; Rüschendorf, Franz; Esparza-Gordillo, Jorge; Medway, Chris W; Mountjoy, Edward; Burrows, Kimberley; Hummel, Oliver; Grosche, Sarah; Brumpton, Ben M; Witte, John S; Hottenga, Jouke-Jan; Willemsen, Gonneke; Zheng, Jie; Rodríguez, Elke; Hotze, Melanie; Franke, Andre; Revez, Joana A; Beesley, Jonathan; Matheson, Melanie C; Dharmage, Shyamali C; Bain, Lisa M; Fritsche, Lars G; Gabrielsen, Maiken E; Balliu, Brunilda; Nielsen, Jonas B; Zhou, Wei; Hveem, Kristian; Langhammer, Arnulf; Holmen, Oddgeir L; Løset, Mari; Abecasis, Gonçalo R; Willer, Cristen J; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Thompson, Philip J; Martin, Nicholas G; Duffy, David L; Novak, Natalija; Schulz, Holger; Karrasch, Stefan; Gieger, Christian; Strauch, Konstantin; Melles, Ronald B; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik K E; Jansen, Rick; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Almqvist, Catarina; Karlsson, Robert; Koppelman, Gerard H; Paternoster, Lavinia

2017-12-01

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10 -8 ), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

PubMed Central

Esparza-Gordillo, Jorge; Medway, Chris W; Mountjoy, Edward; Burrows, Kimberley; Hummel, Oliver; Grosche, Sarah; Brumpton, Ben M; Witte, John S; Hottenga, Jouke-Jan; Willemsen, Gonneke; Zheng, Jie; Rodríguez, Elke; Hotze, Melanie; Franke, Andre; Revez, Joana A; Beesley, Jonathan; Matheson, Melanie C; Dharmage, Shyamali C; Bain, Lisa M; Fritsche, Lars G; Gabrielsen, Maiken E; Balliu, Brunilda; Nielsen, Jonas B; Zhou, Wei; Hveem, Kristian; Langhammer, Arnulf; Holmen, Oddgeir L; Løset, Mari; Abecasis, Gonçalo R; Willer, Cristen J; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Thompson, Philip J; Martin, Nicholas G; Duffy, David L; Novak, Natalija; Schulz, Holger; Karrasch, Stefan; Gieger, Christian; Strauch, Konstantin; Melles, Ronald B; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik KE; Jansen, Rick; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Almqvist, Catarina; Karlsson, Robert; Koppelman, Gerard H; Paternoster, Lavinia

2017-01-01

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2–4. To identify shared risk variants, we performed a genome-wide association study (GWAS, n=360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P<3x10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes. PMID:29083406

Who should pay for bad genes?

PubMed

Rakowski, Eric

2002-10-01

Parents have long been able to influence the genetic composition of their children through their choice of a reproductive partner, if only very approximately. They are, however, increasingly able to determine the genetic make-up of their children in other, more precise ways, such as by selecting a particular gamete or embryo or by genetically modifying an embryo prior to artificial implantation. This Article discusses parents' obligations to their children and other members of the community stemming from their children's genes. In a just state, it argues, parents would be responsible for redressing any genetic disadvantage their children suffer as a result of parents' voluntary actions. Within the context of a liberal egalitarian account of distributive justice, this responsibility might most fairly be discharged through a compulsory insurance plan that provides compensation to genetically disadvantaged children when they might have had non-disadvantaged children instead would in some circumstances incur greater liability, because they could not fairly push the cost of their choices off on other members of the insurance pool. The Article also asks whether parents wrong a child by allowing it to be born with a genetic impairment when, had they taken steps to remove the impairment, the unimpaired child they had would have been a different person from the genetically disadvantaged child because the better-off child's capacities and experiences differed considerably from those that the disadvantaged child would have had. Contrary to many people's moral intuitions, the Article argues that parents do not wrong such a child. Nevertheless, parents remain morally obligated to bear any added costs occasioned by the child's impairment. Any other approach would allow them unjustly to shift the burden of their choices to other parents. Finally, the Article takes up the much debated question of whether parents harm a child by allowing it to be born with a life not worth living when they could have prevented its birth. It suggests that the answer to this question should be irrelevant to parents' legal liability. Acting on behalf of the parental insurance pool, the state may nonetheless adopt a variety of measures to help potential parents avoid giving birth to such children, which one can assume virtually all would prefer.

Association of Major Depressive Disorder with Serum Myeloperoxidase and other Markers of Inflammation: A Twin Study

PubMed Central

Vaccarino, Viola; Brennan, Marie-Luise; Miller, Andrew H.; Bremner, J. Douglas; Ritchie, James C.; Lindau, Frauke; Veledar, Emir; Su, Shaoyong; Murrah, Nancy V.; Jones, Linda; Jawed, Farhan; Dai, Jun; Goldberg, Jack; Hazen, Stanley L.

2008-01-01

Background Major depressive disorder (MDD) has been linked to inflammation, but this association may be due to common precursors to both depression and inflammation. Myeloperoxidase (MPO) is an inflammatory enzyme produced by activated leukocytes which predicts risk of coronary heart disease. We sought to examine whether MPO and other markers of inflammation are associated with MDD, and whether the association is confounded by genetic or other shared familial factors. Methods We examined 178 monozygotic and dizygotic middle-aged male twin pairs. We assessed MDD with the Structured Clinical Interview for Psychiatry Disorders. Blood markers of inflammation included MPO, interleukin-6, white blood cell count, C-reactive protein, tumor necrosis factor (TNF)-α, the TNF-α soluble receptor II, and fibrinogen. Analyses were conducted in the overall sample and among 67 twin pairs discordant for MDD using mixed effects regression. Results Twins with a history of MDD had 32% higher levels of MPO (p<0.0001); this difference persisted after adjusting for other risk factors. Among dizygotic MDD-discordant twin pairs, twins with MDD had 77% higher MPO than their brothers without MDD after adjusting for other factors (p<0.0001). In contrast, no significant association was found in monozygotic twins (p=0.13). Similar, but weaker, associations were found between MDD and other inflammatory biomarkers. Conclusion MPO is a useful biomarker of immune activation in MDD. However, the association between inflammation and MDD is largely due to common genetic liability. Our results are consistent with the hypothesis that genes promoting inflammation are involved in the pathogenesis of MDD. PMID:18514165

The Familial Co-Aggregation of Attention-Deficit/Hyperactivity Disorder and Intellectual Disability: A Register-Based Family Study.

PubMed

Faraone, Stephen V; Ghirardi, Laura; Kuja-Halkola, Ralf; Lichtenstein, Paul; Larsson, Henrik

2017-02-01

Although many studies document an association between attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID), little is known about the etiology of this comorbidity and how it should be addressed in clinical settings. We sought to clarify this issue. All individuals born in Sweden between 1987 and 2006 (n = 2,049,587) were identified using the Medical Birth Register (MBR). From this we selected 7 cohorts of relatives: 1,899,654 parent-offspring pairs, 4,180 monozygotic twin pairs, 12,655 dizygotic twin pairs, 914,848 full sibling pairs, 136,962 maternal half-sibling pairs, 134,502 paternal half-sibling pairs, and 2,790,164 full cousin pairs. We used within-individual and within-family analyses to assess the association between ADHD and ID. Individuals with ID were at increased risk for ADHD compared to those without ID, and relatives of participants with ID were at increased risk of ADHD compared with relatives of those without ID. The magnitude of this association was positively associated with the fraction of the genome shared by the relative pair and was lower for severe compared with mild and moderate ID. Model-fitting analyses demonstrated that 91% of the correlation between the liabilities of ADHD and ID was attributable to genetic factors. These data provide evidence that nearly all of the comorbidity between ADHD and ID can be attributed to genetic factors, which has implications for diagnostic practice. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Shared genetic variance between obesity and white matter integrity in Mexican Americans.

PubMed

Spieker, Elena A; Kochunov, Peter; Rowland, Laura M; Sprooten, Emma; Winkler, Anderson M; Olvera, Rene L; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John; Glahn, David C; Curran, Joanne E

2015-01-01

Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18-81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m(2)) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h (2) = 0.58), WC (h (2) = 0.57), and FA (h (2) = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = -0.25), body (ρG = -0.30), and splenium (ρG = -0.26) of the corpus callosum, internal capsule (ρG = -0.29), and thalamic radiation (ρG = -0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = -0.39, p = 0.020; ρG = -0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors.

Blood pressure and cerebral white matter share common genetic factors in Mexican Americans.

PubMed

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2011-02-01

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9 ± 13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=-0.75; P=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.

Blood Pressure and Cerebral White Matter Share Common Genetic Factors in Mexican-Americans

PubMed Central

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2010-01-01

Elevated arterial pulse pressure (PP) and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially due to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy (FA) of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican-Americans. The patterns of whole-brain and regional genetic overlap between BP and FA were interpreted in the context the pulse-wave encephalopathy (PWE) theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7×1.7×3mm, 55 directions) diffusion tensor imaging (DTI) data were analyzed for 332 (202 females; mean age=47.9±13.3years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements [PP, systolic (SBP) and diastolic (DBP)] and FA (whole-brain and regional values). Intersubject variance in PP and SBP exhibited a significant genetic overlap with variance in whole-brain FA values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=−.75, p=0.01). The pattern of genetic overlap between BP and WM integrity was generally in-agreement with the PWE theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development suggesting a possible role for genotype-by-age interactions. PMID:21135356

Shared genetic basis for migraine and ischemic stroke

PubMed Central

Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S.; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G.; Terwindt, Gisela M.; Sturm, Jonathan; Bis, Joshua C.; Hopewell, Jemma C.; Ferrari, Michel D.; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F.; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I.; Mitchell, Braxton D.; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T.; Kurth, Tobias; Ikram, M. Arfan; Reiner, Alex P.; Longstreth, W.T.; Rothwell, Peter M.; Strachan, David P.; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B.; Davey Smith, George; van Duijn, Cornelia M.; Stefansson, Kari; Worrall, Bradford B.; Nyholt, Dale R.; Markus, Hugh S.; van den Maagdenberg, Arn M.J.M.; Cotsapas, Chris; Zwart, John A.; Palotie, Aarno

2015-01-01

Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10−28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10−20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. PMID:25934857

Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins

PubMed Central

Silberg, Judy L.; Gillespie, Nathan; Moore, Ashlee A.; Eaves, Lindon J.; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

2015-01-01

Objective Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. Method We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Results Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. Conclusions There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children. PMID:25728588

Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins.

PubMed

Silberg, Judy L; Gillespie, Nathan; Moore, Ashlee A; Eaves, Lindon J; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

2015-04-01

Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

Generalists at the interface: Nematode transmission between wild and domestic ungulates.

PubMed

Walker, Josephine G; Morgan, Eric R

2014-12-01

Many parasitic nematode species are generalists capable of infecting multiple host species. The complex life cycle of nematodes, involving partial development outside of the host, facilitates transmission of these parasites between host species even when there is no direct contact between hosts. Infective nematode larvae persist in the environment, and where grazing or water sources are shared ingestion of parasite larvae deposited by different host species is likely. In this paper we examine the extent to which nematode parasite species have been observed in sympatric wild and domestic ungulates. First, using existing host-parasite databases, we describe expected overlap of 412 nematode species between 76 wild and 8 domestic ungulate host species. Our results indicate that host-specific parasites make up less than half of the nematode parasites infecting any particular ungulate host species. For wild host species, between 14% (for common warthog) and 76% (for mouflon) of parasitic nematode species are shared with domestic species. For domestic host species, between 42% (for horse) and 77% (for llamas/alpacas) of parasitic nematode species are shared with wild species. We also present an index of liability to describe the risk of cross-boundary parasites to each host species. We then examine specific examples from the literature in which transmission of nematode parasites between domestic and wild ungulates is described. However, there are many limitations in the existing data due to geographical bias and certain host species being studied more frequently than others. Although we demonstrate that many species of parasitic nematode are found in both wild and domestic hosts, little work has been done to demonstrate whether transmission is occurring between species or whether similar strains circulate separately. Additional research on cross-species transmission, including the use of models and of genetic methods to define strains, will provide evidence to answer this question.

Generalists at the interface: Nematode transmission between wild and domestic ungulates

PubMed Central

Walker, Josephine G.; Morgan, Eric R.

2014-01-01

Many parasitic nematode species are generalists capable of infecting multiple host species. The complex life cycle of nematodes, involving partial development outside of the host, facilitates transmission of these parasites between host species even when there is no direct contact between hosts. Infective nematode larvae persist in the environment, and where grazing or water sources are shared ingestion of parasite larvae deposited by different host species is likely. In this paper we examine the extent to which nematode parasite species have been observed in sympatric wild and domestic ungulates. First, using existing host–parasite databases, we describe expected overlap of 412 nematode species between 76 wild and 8 domestic ungulate host species. Our results indicate that host-specific parasites make up less than half of the nematode parasites infecting any particular ungulate host species. For wild host species, between 14% (for common warthog) and 76% (for mouflon) of parasitic nematode species are shared with domestic species. For domestic host species, between 42% (for horse) and 77% (for llamas/alpacas) of parasitic nematode species are shared with wild species. We also present an index of liability to describe the risk of cross-boundary parasites to each host species. We then examine specific examples from the literature in which transmission of nematode parasites between domestic and wild ungulates is described. However, there are many limitations in the existing data due to geographical bias and certain host species being studied more frequently than others. Although we demonstrate that many species of parasitic nematode are found in both wild and domestic hosts, little work has been done to demonstrate whether transmission is occurring between species or whether similar strains circulate separately. Additional research on cross-species transmission, including the use of models and of genetic methods to define strains, will provide evidence to answer this question. PMID:25426420

Investigating genetic and environmental contributions to adolescent externalizing behavior in a collectivistic culture: a multi-informant twin study.

PubMed

Chen, J; Yu, J; Zhang, J; Li, X; McGue, M

2015-07-01

Little is known about the etiology of adolescents' externalizing behavior (Ext) in collectivistic cultures. We aimed to fill this gap by investigating the genetic and environmental influences on Ext in Chinese adolescents. The etiological heterogeneity of aggression (AGG) and rule breaking (RB) was also examined. The study sample included 908 pairs of same-sex twins aged from 10 to 18 years (mean = 13.53 years, s.d. = 2.26). Adolescents' Ext were assessed with the Achenbach System of Empirically Based Assessment including Child Behavior Checklist, Teacher Report Form, and Youth Self-Report. Univariate genetic analyses showed that genetic influences on all measures were moderate ranging from 34% to 50%, non-shared environmental effects ranged from 23% to 52%, and shared environmental effects were significant in parent- and teacher-reported measures ranging from 29% to 43%. Bivariate genetic analyses indicated that AGG and RB shared large genetic influences (r g = 0.64-0.79) but moderate non-shared environmental factors (r e = 0.34-0.52). Chinese adolescents' Ext was moderately influenced by genetic factors. AGG and RB had moderate independent genetic and non-shared environmental influences, and thus constitute etiologically distinct dimensions within Ext in Chinese adolescents. The heritability of AGG, in particular, was smaller in Chinese adolescents than suggested by previous data obtained on Western peers. This study suggests that the collectivistic cultural values and Confucianism philosophy may attenuate genetic potential in Ext, especially AGG.

Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II

PubMed Central

Koenen, Karestan C; DeVivo, Immaculata; Rich-Edwards, Janet; Smoller, Jordan W; Wright, Rosalind J; Purcell, Shaun M

2009-01-01

Background One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder. Methods and design We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD. The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach. Discussion Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations. PMID:19480706

A multivariate twin study of early literacy in Japanese Kana

PubMed Central

Fujisawa, Keiko K.; Wadsworth, Sally J.; Kakihana, Shinichiro; Olson, Richard K.; DeFries, John C.; Byrne, Brian; Ando, Juko

2013-01-01

This first Japanese twin study of early literacy development investigated the extent to which genetic and environmental factors influence individual differences in prereading skills in 238 pairs of twins at 42 months of age. Twin pairs were individually tested on measures of phonological awareness, kana letter name/sound knowledge, receptive vocabulary, visual perception, nonword repetition, and digit span. Results obtained from univariate behavioral-genetic analyses yielded little evidence for genetic influences, but substantial shared-environmental influences, for all measures. Phenotypic confirmatory factor analysis suggested three correlated factors: phonological awareness, letter name/sound knowledge, and general prereading skills. Multivariate behavioral genetic analyses confirmed relatively small genetic and substantial shared environmental influences on the factors. The correlations among the three factors were mostly attributable to shared environment. Thus, shared environmental influences play an important role in the early reading development of Japanese children. PMID:23997545

Mapping quantitative trait loci for binary trait in the F2:3 design.

PubMed

Zhu, Chengsong; Zhang, Yuan-Ming; Guo, Zhigang

2008-12-01

In the analysis of inheritance of quantitative traits with low heritability, an F(2:3) design that genotypes plants in F(2) and phenotypes plants in F(2:3) progeny is often used in plant genetics. Although statistical approaches for mapping quantitative trait loci (QTL) in the F(2:3) design have been well developed, those for binary traits of biological interest and economic importance are seldom addressed. In this study, an attempt was made to map binary trait loci (BTL) in the F(2:3) design. The fundamental idea was: the F(2) plants were genotyped, all phenotypic values of each F(2:3) progeny were measured for binary trait, and these binary trait values and the marker genotype informations were used to detect BTL under the penetrance and liability models. The proposed method was verified by a series of Monte-Carlo simulation experiments. These results showed that maximum likelihood approaches under the penetrance and liability models provide accurate estimates for the effects and the locations of BTL with high statistical power, even under of low heritability. Moreover, the penetrance model is as efficient as the liability model, and the F(2:3) design is more efficient than classical F(2) design, even though only a single progeny is collected from each F(2:3) family. With the maximum likelihood approaches under the penetrance and the liability models developed in this study, we can map binary traits as we can do for quantitative trait in the F(2:3) design.

Empathy as a “Risky Strength”: A Multilevel Examination of Empathy and Risk for Internalizing Disorders

PubMed Central

Tone, Erin B.; Tully, Erin C.

2015-01-01

Learning to respond to others’ distress with well-regulated empathy is an important developmental task linked to positive health outcomes and moral achievements. However, this important interpersonal skill set may also, paradoxically, confer risk for depression and anxiety when present at extreme levels and in combination with certain individual characteristics or within particular contexts. The purpose of this review is to describe an empirically-grounded theoretical rationale for the hypothesis that empathic tendencies can be “risky strengths”. We propose a model in which typical development of affective and cognitive empathy can be influenced by complex interplay among intraindividual and interindividual moderators that increase risk for empathic personal distress and excessive interpersonal guilt. These intermediate states, in turn, precipitate internalizing problems that map onto empirically-derived fear/arousal and anhedonia/misery subfactors of internalizing disorders. The intraindividual moderators include a genetically-influenced propensity toward physiological hyperarousal, which is proposed to interact with genetic propensity to empathic sensitivity to contribute to neurobiological processes that underlie personal distress responses others’ pain or unhappiness. This empathic personal distress then increases risk for internalizing problems, particularly fear/arousal symptoms. Similarly, interactions between genetic propensities toward negative thinking processes and empathic sensitivity are hypothesized to contribute to excess interpersonal guilt in response to others’ distress. In turn, this interpersonal guilt increases risk for internalizing problems, especially anhedonia/misery symptoms. Interindividual moderators, such as maladaptive parenting or chronic exposure to parents’ negative affect, further interact with these genetic liabilities to amplify risk for personal distress and interpersonal guilt, as well as for consequent internalizing problems. Age-related increases in the heritability of depression, anxiety, and empathy-related constructs are consistent with developmental shifts toward greater influence of intraindividual moderators throughout childhood and adolescence, with interindividual moderators exerting their greatest influence during early childhood. Efforts to modulate neurobiological and behavioral expressions of genetic dysregulation liabilities and to promote adaptive empathic skills must thus begin early in development. PMID:25422978

Empathy as a "risky strength": a multilevel examination of empathy and risk for internalizing disorders.

PubMed

Tone, Erin B; Tully, Erin C

2014-11-01

Learning to respond to others' distress with well-regulated empathy is an important developmental task linked to positive health outcomes and moral achievements. However, this important interpersonal skill set may also confer risk for depression and anxiety when present at extreme levels and in combination with certain individual characteristics or within particular contexts. The purpose of this review is to describe an empirically grounded theoretical rationale for the hypothesis that empathic tendencies can be "risky strengths." We propose a model in which typical development of affective and cognitive empathy can be influenced by complex interplay among intraindividual and interindividual moderators that increase risk for empathic personal distress and excessive interpersonal guilt. These intermediate states in turn precipitate internalizing problems that map onto empirically derived fear/arousal and anhedonia/misery subfactors of internalizing disorders. The intraindividual moderators include a genetically influenced propensity toward physiological hyperarousal, which is proposed to interact with genetic propensity to empathic sensitivity to contribute to neurobiological processes that underlie personal distress responses to others' pain or unhappiness. This empathic personal distress then increases risk for internalizing problems, particularly fear/arousal symptoms. In a similar fashion, interactions between genetic propensities toward negative thinking processes and empathic sensitivity are hypothesized to contribute to excess interpersonal guilt in response to others' distress. This interpersonal guilt then increases the risk for internalizing problems, especially anhedonia/misery symptoms. Interindividual moderators, such as maladaptive parenting or chronic exposure to parents' negative affect, further interact with these genetic liabilities to amplify risk for personal distress and interpersonal guilt as well as for consequent internalizing problems. Age-related increases in the heritability of depression, anxiety, and empathy-related constructs are consistent with developmental shifts toward greater influence of intraindividual moderators throughout childhood and adolescence, with interindividual moderators exerting their greatest influence during early childhood. Efforts to modulate neurobiological and behavioral expressions of genetic dysregulation liabilities and to promote adaptive empathic skills must thus begin early in development.

Genetics and pharmacogenetics of mood disorders.

PubMed

Serretti, Alessandro

2017-04-30

Genetic research in Psychiatry is viewed by clinicians with both hope and curiosity sometimes mixed with disillusionment. Indeed, in the last 30 years many results have not been confirmed and clinical applications are still missing. However recent findings suggest that we are at the beginning of a new era. A set of variants within neuroplasticity and inflammation genes have been identified as a valid basis for both bipolar disorder and major depression. Similarly, a set of genes has been identified as a liability factor for response and tolerability to antidepressants and the first clinical applications are already in the market. However, some caution should be applied until definite findings are available.

Contributions of Genes and Environment to Developmental Change in Alcohol Use.

PubMed

Long, E C; Verhulst, B; Aggen, S H; Kendler, K S; Gillespie, N A

2017-09-01

The precise nature of how genetic and environmental risk factors influence changes in alcohol use (AU) over time has not yet been investigated. Therefore, the aim of the present study is to examine the nature of longitudinal changes in these risk factors to AU from mid-adolescence through young adulthood. Using a large sample of male twins, we compared five developmental models that each makes different predictions regarding the longitudinal changes in genetic and environmental risks for AU. The best-fitting model indicated that genetic influences were consistent with a gradual growth in the liability to AU, whereas unique environmental risk factors were consistent with an accumulation of risks across time. These results imply that two distinct processes influence adolescent AU between the ages of 15-25. Genetic effects influence baseline levels of AU and rates of change across time, while unique environmental effects are more cumulative.

Advances in Autism

PubMed Central

Geschwind, Daniel H.

2013-01-01

Autism is a common childhood neurodevelopmental disorder with strong genetic liability. It is not a unitary entity but a clinical syndrome, with variable deficits in social behavior and language, restrictive interests, and repetitive behaviors. Recent advances in the genetics of autism emphasize its etiological heterogeneity, with each genetic susceptibility locus accounting for only a small fraction of cases or having a small effect. Therefore, it is not surprising that no unifying structural or neuropathological features have been conclusively identified. Given the heterogeneity of autism spectrum disorder (ASD), approaches based on studying heritable components of the disorder, or endophenotypes, such as language or social cognition, provide promising avenues for genetic and neurobiological investigations. Early intensive behavioral and cognitive interventions are efficacious in many cases, but autism does not remit in the majority of children. Therefore, development of targeted therapies based on pathophysiologically and etiologically defined subtypes of ASD remains an important and achievable goal of current research. PMID:19630577

Consequences of transmission of solar energy from outer space

NASA Astrophysics Data System (ADS)

Cocca, A. A.

The possible physical effects of MW, laser, or mirror-type SPS transmissions and their legal implications are considered. The bioeffects of the transmitted radiation and the atmospheric effects of transmission and of launcher-effluent injection (heating and ionospheric depletion) are examined, and the political aspects of receiver siting (near the equator for GEO solar systems) are indicated. The occupation of large portions of the MW band for SPS transmission and more generalized detrimental effects of SPS on space and terrestrial communications systems are explored, and the provisions of the Space Treaty, the Liability Convention, and (proposed) WARC Radio Regulations are discussed. Since no specific regulations on the use of solar energy have been adopted, a set of twelve basic tenets is proposed. The definition of solar energy and the GEO as nonappropriable parts of the 'common heritage of mankind' and the establishment of international organs (including a compulsory tribunal) to enforce the liability of SPS operators for ensuing damages and the fair sharing of soar resources are urged.

Open sharing of genomic data: Who does it and why?

PubMed

Haeusermann, Tobias; Greshake, Bastian; Blasimme, Alessandro; Irdam, Darja; Richards, Martin; Vayena, Effy

2017-01-01

We explored the characteristics and motivations of people who, having obtained their genetic or genomic data from Direct-To-Consumer genetic testing (DTC-GT) companies, voluntarily decide to share them on the publicly accessible web platform openSNP. The study is the first attempt to describe open data sharing activities undertaken by individuals without institutional oversight. In the paper we provide a detailed overview of the distribution of the demographic characteristics and motivations of people engaged in genetic or genomic open data sharing. The geographical distribution of the respondents showed the USA as dominant. There was no significant gender divide, the age distribution was broad, educational background varied and respondents with and without children were equally represented. Health, even though prominent, was not the respondents' primary or only motivation to be tested. As to their motivations to openly share their data, 86.05% indicated wanting to learn about themselves as relevant, followed by contributing to the advancement of medical research (80.30%), improving the predictability of genetic testing (76.02%) and considering it fun to explore genotype and phenotype data (75.51%). Whereas most respondents were well aware of the privacy risks of their involvement in open genetic data sharing and considered the possibility of direct, personal repercussions troubling, they estimated the risk of this happening to be negligible. Our findings highlight the diversity of DTC-GT consumers who decide to openly share their data. Instead of focusing exclusively on health-related aspects of genetic testing and data sharing, our study emphasizes the importance of taking into account benefits and risks that stretch beyond the health spectrum. Our results thus lend further support to the call for a broader and multi-faceted conceptualization of genomic utility.

Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders.

PubMed

Venables, Noah C; Hicks, Brian M; Yancey, James R; Kramer, Mark D; Nelson, Lindsay D; Strickland, Casey M; Krueger, Robert F; Iacono, William G; Patrick, Christopher J

2017-05-01

Threat sensitivity (THT) and weak inhibitory control (or disinhibition; DIS) are trait constructs that relate to multiple types of psychopathology and can be assessed psychoneurometrically (i.e., using self-report and physiological indicators combined). However, to establish that psychoneurometric assessments of THT and DIS index biologically-based liabilities, it is important to clarify the etiologic bases of these variables and their associations with clinical problems. The current work addressed this important issue using data from a sample of identical and fraternal adult twins (N=454). THT was quantified using a scale measure and three physiological indicators of emotional reactivity to visual aversive stimuli. DIS was operationalized using scores on two scale measures combined with two brain indicators from cognitive processing tasks. THT and DIS operationalized in these ways both showed appreciable heritability (0.45, 0.68), and genetic variance in these traits accounted for most of their phenotypic associations with fear, distress, and substance use disorder symptoms. Our findings suggest that, as indices of basic dispositional liabilities for multiple forms of psychopathology with direct links to neurophysiology, psychoneurometric assessments of THT and DIS represent novel and important targets for biologically-oriented research on psychopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic modelling in schizophrenia according to HLA typing.

PubMed

Smeraldi, E; Macciardi, F; Gasperini, M; Orsini, A; Bellodi, L; Fabio, G; Morabito, A

1986-09-01

Studying families of schizophrenic patients, we observed that the risk of developing the overt form of the illness could be enhanced by some factors. Among these various factors we focused our attention on a biological variable, namely the presence or the absence of particular HLA antigens: partitioning our schizophrenic patients according to their HLA structure (i.e. those with HLA-A1 or CRAG-A1 antigens and those with HLA-non-CRAG-A1 antigens, respectively), revealed different illness distribution in the two groups. From a genetic point of view, this finding suggests the presence of heterogeneity in the hypothetical liability system related to schizophrenia and we evaluated the heterogeneity hypothesis by applying alternative genetic models to our data, trying to detect more biologically homogeneous subgroups of the disease.

A behavioral genetic analysis of callous-unemotional traits and Big Five personality in adolescence.

PubMed

Mann, Frank D; Briley, Daniel A; Tucker-Drob, Elliot M; Harden, K Paige

2015-11-01

Callous-unemotional (CU) traits, such as lacking empathy and emotional insensitivity, predict the onset, severity, and persistence of antisocial behavior. CU traits are heritable, and genetic influences on CU traits contribute to antisocial behavior. This study examines genetic overlap between CU traits and general domains of personality. We measured CU traits using the Inventory of Callous-Unemotional Traits (ICU) and Big Five personality using the Big Five Inventory in a sample of adolescent twins from the Texas Twin Project. Genetic influences on the Big Five personality dimensions could account for the entirety of genetic influences on CU traits. Item Response Theory results indicate that the Inventory of Callous and Unemotional Traits is better at detecting clinically relevant personality variation at lower extremes of personality trait continua, particularly low agreeableness and low conscientiousness. The proximate biological mechanisms that mediate genetic liabilities for CU traits remain an open question. The results of the current study suggest that understanding the development of normal personality may inform understanding of the genetic underpinnings of callous and unemotional behavior. (c) 2015 APA, all rights reserved).

Shared genetic variance between obesity and white matter integrity in Mexican Americans

PubMed Central

Spieker, Elena A.; Kochunov, Peter; Rowland, Laura M.; Sprooten, Emma; Winkler, Anderson M.; Olvera, Rene L.; Almasy, Laura; Duggirala, Ravi; Fox, Peter T.; Blangero, John; Glahn, David C.; Curran, Joanne E.

2015-01-01

Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = −0.25), body (ρG = −0.30), and splenium (ρG = −0.26) of the corpus callosum, internal capsule (ρG = −0.29), and thalamic radiation (ρG = −0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = −0.39, p = 0.020; ρG = −0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors. PMID:25763009

Psychometric modeling of abuse and dependence symptoms across six illicit substances indicates novel dimensions of misuse

PubMed Central

Clark, Shaunna L.; Gillespie, Nathan A.; Adkins, Daniel E.; Kendler, Kenneth S.; Neale, Michael C.

2015-01-01

Aims This study explored the factor structure of DSM III-R/IV symptoms for substance abuse and dependence across six illicit substance categories in a population-based sample of males. Method DSM III-R/IV drug abuse and dependence symptoms for cannabis, sedatives, stimulants, cocaine, opioids and hallucinogens from 4179 males born 1940-1970 from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders were analyzed. Confirmatory factor analyses tested specific hypotheses regarding the latent structure of substance misuse for a comprehensive battery of 13 misuse symptoms measured across six illicit substance categories (78 items). Results Among the models fit, the latent structure of substance misuse was best represented by a combination of substance-specific factors and misuse symptom-specific factors. We found no support for a general liability factor to illicit substance misuse. Conclusions Results indicate that liability to misuse illicit substances is drug class specific, with little evidence for a general liability factor. Additionally, unique dimensions capturing propensity toward specific misuse symptoms (e.g., tolerance, withdrawal) across substances were identified. While this finding requires independent replication, the possibility of symptom-specific misuse factors, present in multiple substances, raises the prospect of genetic, neurobiological and behavioral predispositions toward distinct, narrowly defined features of drug abuse and dependence. PMID:26517709

Common liability to addiction and “gateway hypothesis”: Theoretical, empirical and evolutionary perspective

PubMed Central

Vanyukov, Michael M.; Tarter, Ralph E.; Kirillova, Galina P.; Kirisci, Levent; Reynolds, Maureen D.; Kreek, Mary Jeanne; Conway, Kevin P.; Maher, Brion S.; Iacono, William G.; Bierut, Laura; Neale, Michael C.; Clark, Duncan B.; Ridenour, Ty A.

2013-01-01

Background Two competing concepts address the development of involvement with psychoactive substances: the “gateway hypothesis” (GH) and common liability to addiction (CLA). Method The literature on theoretical foundations and empirical findings related to both concepts is reviewed. Results The data suggest that drug use initiation sequencing, the core GH element, is variable and opportunistic rather than uniform and developmentally deterministic. The association between risks for use of different substances, if any, can be more readily explained by common underpinnings than by specific staging. In contrast, the CLA concept is grounded in genetic theory and supported by data identifying common sources of variation in the risk for specific addictions. This commonality has identifiable neurobiological substrate and plausible evolutionary explanations. Conclusions Whereas the “gateway” hypothesis does not specify mechanistic connections between “stages”, and does not extend to the risks for addictions, the concept of common liability to addictions incorporates sequencing of drug use initiation as well as extends to related addictions and their severity, provides a parsimonious explanation of substance use and addiction co-occurrence, and establishes a theoretical and empirical foundation to research in etiology, quantitative risk and severity measurement, as well as targeted non-drug-specific prevention and early intervention. PMID:22261179

Early Origins of Autism Comorbidity: Neuropsychiatric Traits Correlated in Childhood Are Independent in Infancy.

PubMed

Hawks, Zoë W; Marrus, Natasha; Glowinski, Anne L; Constantino, John N

2018-03-16

Previous research has suggested that behavioral comorbidity is the rule rather than the exception in autism. The present study aimed to trace the respective origins of autistic and general psychopathologic traits-and their association-to infancy. Measurements of autistic traits and early liability for general psychopathology were assessed in 314 twins at 18 months, ascertained from the general population using birth records. 222 twins were re-evaluated at 36 months. Standardized ratings of variation in social communication at 18 months were highly heritable and strongly predicted autistic trait scores at 36 months. These early indices of autistic liability were independent from contemporaneous ratings of behavior problems on the Brief Infant-Toddler Social and Emotional Assessment (which were substantially environmentally-influenced), and did not meaningfully predict internalizing or externalizing scores on the Achenbach Scales of Empirically Based Assessment at 36 months. In this general population infant twin study, variation in social communication was independent from variation in other domains of general psychopathology, and exhibited a distinct genetic structure. The commonly-observed comorbidity of specific psychiatric syndromes with autism may arise from subsequent interactions between autistic liability and independent susceptibilities to other psychopathologic traits, suggesting opportunities for preventive amelioration of outcomes of these interactions over the course of development.

Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.

PubMed

Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G; Terwindt, Gisela M; Sturm, Jonathan; Bis, Joshua C; Hopewell, Jemma C; Ferrari, Michel D; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I; Mitchell, Braxton D; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T; Kurth, Tobias; Ikram, M Arfan; Reiner, Alex P; Longstreth, W T; Rothwell, Peter M; Strachan, David P; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B; Davey Smith, George; van Duijn, Cornelia M; Stefansson, Kari; Worrall, Bradford B; Nyholt, Dale R; Markus, Hugh S; van den Maagdenberg, Arn M J M; Cotsapas, Chris; Zwart, John A; Palotie, Aarno; Dichgans, Martin

2015-05-26

To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10(-20) for the CE score in MO). Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. © 2015 American Academy of Neurology.

Public and Biobank Participant Attitudes toward Genetic Research Participation and Data Sharing

PubMed Central

Lemke, A.A.; Wolf, W.A.; Hebert-Beirne, J.; Smith, M.E.

2010-01-01

Research assessing attitudes toward consent processes for high-throughput genomic-wide technologies and widespread sharing of data is limited. In order to develop a better understanding of stakeholder views toward these issues, this cross-sectional study assessed public and biorepository participant attitudes toward research participation and sharing of genetic research data. Forty-nine individuals participated in 6 focus groups; 28 in 3 public focus groups and 21 in 3 NUgene biorepository participant focus groups. In the public focus groups, 75% of participants were women, 75% had some college education or more, 46% were African-American and 29% were Hispanic. In the NUgene focus groups, 67% of participants were women, 95% had some college education or more, and the majority (76%) of participants was Caucasian. Five major themes were identified in the focus group data: (a) a wide spectrum of understanding of genetic research; (b) pros and cons of participation in genetic research; (c) influence of credibility and trust of the research institution; (d) concerns about sharing genetic research data and need for transparency in the Policy for Sharing of Data in National Institutes of Health-Supported or Conducted Genome-Wide Association Studies; (e) a need for more information and education about genetic research. In order to increase public understanding and address potential concerns about genetic research, future efforts should be aimed at involving the public in genetic research policy development and in identifying or developing appropriate educational strategies to meet the public's needs. PMID:20805700

The growth and gaps of genetic data sharing policies in the United States

PubMed Central

Arias, Jalayne J.; Pham-Kanter, Genevieve; Campbell, Eric G.

2014-01-01

The 1996 Bermuda Principles launched a new era in data sharing, reflecting a growing belief that the rapid public dissemination of research data was crucial to scientific progress in genetics. A historical review of data sharing policies in the field of genetics and genomics reflects changing scientific norms and evolving views of genomic data, particularly related to human subjects’ protections and privacy concerns. The 2013 NIH Draft Genomic Data Sharing (GDS) Policy incorporates the most significant protections and guidelines to date. The GDS Policy, however, will face difficult challenges ahead as geneticists seek to balance the very real concerns of research participants and the scientific norms that propel research forward. This article provides a novel evaluation of genetic and GDS policies’ treatment of human subjects’ protections. The article examines not only the policies, but also some of the most pertinent scientific, legal, and regulatory developments that occurred alongside data sharing policies. This historical perspective highlights the challenges that future data sharing policies, including the recently disseminated NIH GDS Draft Policy, will encounter. PMID:27774180

Inherited behavioral susceptibility to adiposity in infancy: a multivariate genetic analysis of appetite and weight in the Gemini birth cohort.

PubMed

Llewellyn, Clare H; van Jaarsveld, Cornelia H M; Plomin, Robert; Fisher, Abigail; Wardle, Jane

2012-03-01

The behavioral susceptibility model proposes that inherited differences in traits such as appetite confer differential risk of weight gain and contribute to the heritability of weight. Evidence that the FTO gene may influence weight partly through its effects on appetite supports this model, but testing the behavioral pathways for multiple genes with very small effects is not feasible. Twin analyses make it possible to get a broad-based estimate of the extent of shared genetic influence between appetite and weight. The objective was to use multivariate twin analyses to test the hypothesis that associations between appetite and weight are underpinned by shared genetic effects. Data were from Gemini, a population-based birth cohort of twins (n = 4804) born in 2007. Infant weights at 3 mo were taken from the records of health professionals. Appetite was assessed at 3 mo for the milk-feeding period by using the Baby Eating Behaviour Questionnaire (BEBQ), a parent-reported measure of appetite [enjoyment of food, food responsiveness, slowness in eating (SE), satiety responsiveness (SR), and appetite size (AS)]. Multivariate quantitative genetic modeling was used to test for shared genetic influences. Significant correlations were found between all BEBQ traits and weight. Significant shared genetic influence was identified for weight with SE, SR, and AS; genetic correlations were between 0.22 and 0.37. Shared genetic effects explained 41-45% of these phenotypic associations. Differences in weight in infancy may be due partly to genetically determined differences in appetitive traits that confer differential susceptibility to obesogenic environments.

Shared genetic influences on negative emotionality and major depression/conduct disorder comorbidity.

PubMed

Tackett, Jennifer L; Waldman, Irwin D; Van Hulle, Carol A; Lahey, Benjamin B

2011-08-01

To investigate whether genetic contributions to major depressive disorder and conduct disorder comorbidity are shared with genetic influences on negative emotionality. Primary caregivers of 2,022 same- and opposite-sex twin pairs 6 to 18 years of age comprised a population-based sample. Participants were randomly selected across five regions in Tennessee, with stratification by age and geographic location. Face-to-face structured interviews were conducted with the primary caregiver of a representative sample of twins. After accounting for genetic influences on negative emotionality, genetic influences on major depressive disorder/conduct disorder comorbidity were nonsignficant, but only in male twins. Specifically, 19% of the variance in the two disorders was accounted for by genetic factors shared with negative emotionality in male twins. Although the full hypothesis could not be tested in female twins, 10% to 11% of the variance in the two disorders was also accounted for by genetic factors shared with negative emotionality. Common shared environmental and nonshared environmental influences were found for major depressive disorder/conduct disorder comorbidity in male and female twins. Negative emotionality represents an important dispositional trait that may explain genetic influences on major depressive disorder/conduct disorder comorbidity, at least for boys. Models of major depressive disorder/conduct disorder comorbidity must simultaneously measure common and specific genetic and environmental factors for a full understanding of this phenomenon. Gender differences require specific research attention in dispositional factors and developmental progression. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic liability for diabetic phenotypes

PubMed Central

Multhaup, Michael L.; Seldin, Marcus; Jaffe, Andrew E.; Lei, Xia; Kirchner, Henriette; Mondal, Prosenjit; Li, Yuanyuan; Rodriguez, Varenka; Drong, Alexander; Hussain, Mehboob; Lindgren, Cecilia; McCarthy, Mark; Näslund, Erik; Zierath, Juleen R.; Wong, G. William; Feinberg, Andrew P.

2015-01-01

SUMMARY Using a functional approach to investigate the epigenetics of Type 2 Diabetes (T2D), we combine three lines of evidence – diet-induced epigenetic dysregulation in mouse, epigenetic conservation in humans, and T2D clinical risk evidence – to identify genes implicated in T2D pathogenesis through epigenetic mechanisms related to obesity. Beginning with dietary manipulation of genetically homogeneous mice, we identify differentially DNA-methylated genomic regions. We then replicate these results in adipose samples from lean and obese patients pre- and post-Roux-en-Y gastric bypass, identifying regions where both the location and direction of methylation change is conserved. These regions overlap with 27 genetic T2D risk loci, only one of which was deemed significant by GWAS alone. Functional analysis of genes associated with these regions revealed four genes with roles in insulin resistance, demonstrating the potential general utility of this approach for complementing conventional human genetic studies by integrating cross-species epigenomics and clinical genetic risk. PMID:25565211

The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.

PubMed

Shaw, Liam; Ribeiro, Andre L R; Levine, Adam P; Pontikos, Nikolas; Balloux, Francois; Segal, Anthony W; Roberts, Adam P; Smith, Andrew M

2017-09-12

The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition. IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years. Copyright © 2017 Shaw et al.

Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders.

PubMed

Volk, D W; Sampson, A R; Zhang, Y; Edelson, J R; Lewis, D A

2016-09-01

Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a 'low GABA marker' (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders. Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects. Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype. These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia: A Danish Population-Based Study and Meta-analysis.

PubMed

Agerbo, Esben; Sullivan, Patrick F; Vilhjálmsson, Bjarni J; Pedersen, Carsten B; Mors, Ole; Børglum, Anders D; Hougaard, David M; Hollegaard, Mads V; Meier, Sandra; Mattheisen, Manuel; Ripke, Stephan; Wray, Naomi R; Mortensen, Preben B

2015-07-01

Schizophrenia has a complex etiology influenced both by genetic and nongenetic factors but disentangling these factors is difficult. To estimate (1) how strongly the risk for schizophrenia relates to the mutual effect of the polygenic risk score, parental socioeconomic status, and family history of psychiatric disorders; (2) the fraction of cases that could be prevented if no one was exposed to these factors; (3) whether family background interacts with an individual's genetic liability so that specific subgroups are particularly risk prone; and (4) to what extent a proband's genetic makeup mediates the risk associated with familial background. We conducted a nested case-control study based on Danish population-based registers. The study consisted of 866 patients diagnosed as having schizophrenia between January 1, 1994, and December 31, 2006, and 871 matched control individuals. Genome-wide data and family psychiatric and socioeconomic background information were obtained from neonatal biobanks and national registers. Results from a separate meta-analysis (34,600 cases and 45,968 control individuals) were applied to calculate polygenic risk scores. Polygenic risk scores, parental socioeconomic status, and family psychiatric history. Odds ratios (ORs), attributable risks, liability R2 values, and proportions mediated. Schizophrenia was associated with the polygenic risk score (OR, 8.01; 95% CI, 4.53-14.16 for highest vs lowest decile), socioeconomic status (OR, 8.10; 95% CI, 3.24-20.3 for 6 vs no exposures), and a history of schizophrenia/psychoses (OR, 4.18; 95% CI, 2.57-6.79). The R2 values were 3.4% (95% CI, 2.1-4.6) for the polygenic risk score, 3.1% (95% CI, 1.9-4.3) for parental socioeconomic status, and 3.4% (95% CI, 2.1-4.6) for family history. Socioeconomic status and psychiatric history accounted for 45.8% (95% CI, 36.1-55.5) and 25.8% (95% CI, 21.2-30.5) of cases, respectively. There was an interaction between the polygenic risk score and family history (P = .03). A total of 17.4% (95% CI, 9.1-26.6) of the effect associated with family history of schizophrenia/psychoses was mediated through the polygenic risk score. Schizophrenia was associated with the polygenic risk score, family psychiatric history, and socioeconomic status. Our study demonstrated that family history of schizophrenia/psychoses is partly mediated through the individual's genetic liability.

Implications of genome wide association studies for addiction: are our a priori assumptions all wrong?

PubMed

Hall, F Scott; Drgonova, Jana; Jain, Siddharth; Uhl, George R

2013-12-01

Substantial genetic contributions to addiction vulnerability are supported by data from twin studies, linkage studies, candidate gene association studies and, more recently, Genome Wide Association Studies (GWAS). Parallel to this work, animal studies have attempted to identify the genes that may contribute to responses to addictive drugs and addiction liability, initially focusing upon genes for the targets of the major drugs of abuse. These studies identified genes/proteins that affect responses to drugs of abuse; however, this does not necessarily mean that variation in these genes contributes to the genetic component of addiction liability. One of the major problems with initial linkage and candidate gene studies was an a priori focus on the genes thought to be involved in addiction based upon the known contributions of those proteins to drug actions, making the identification of novel genes unlikely. The GWAS approach is systematic and agnostic to such a priori assumptions. From the numerous GWAS now completed several conclusions may be drawn: (1) addiction is highly polygenic; each allelic variant contributing in a small, additive fashion to addiction vulnerability; (2) unexpected, compared to our a priori assumptions, classes of genes are most important in explaining addiction vulnerability; (3) although substantial genetic heterogeneity exists, there is substantial convergence of GWAS signals on particular genes. This review traces the history of this research; from initial transgenic mouse models based upon candidate gene and linkage studies, through the progression of GWAS for addiction and nicotine cessation, to the current human and transgenic mouse studies post-GWAS. © 2013.

7 CFR 1400.204 - Limited partnerships, limited liability partnerships, limited liability companies, corporations...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Limited partnerships, limited liability partnerships..., limited liability partnerships, limited liability companies, corporations, and other similar legal entities. (a) A limited partnership, limited liability partnership, limited liability company, corporation...

Shared Genetic Influences on Negative Emotionality and Major Depression/Conduct Disorder Comorbidity

ERIC Educational Resources Information Center

Tackett, Jennifer L.; Waldman, Irwin D.; Van Hulle, Carol A.; Lahey, Benjamin B.

2011-01-01

Objective: To investigate whether genetic contributions to major depressive disorder and conduct disorder comorbidity are shared with genetic influences on negative emotionality. Method: Primary caregivers of 2,022 same- and opposite-sex twin pairs 6 to 18 years of age comprised a population-based sample. Participants were randomly selected across…

Research review: the shared environment as a key source of variability in child and adolescent psychopathology.

PubMed

Burt, S Alexandra

2014-04-01

Behavioral genetic research has historically concluded that the more important environmental influences were nonshared or result in differences between siblings, whereas environmental influences that create similarities between siblings (referred to as shared environmental influences) were indistinguishable from zero. Recent theoretical and meta-analytic work {Burt. Psychological Bulletin [135 (2009) 608]} has challenged this conclusion as it relates to child and adolescent psychopathology, however, arguing that the shared environment is a moderate, persistent, and identifiable source of individual differences in such outcomes prior to adulthood. The current review seeks to bolster research on the shared environment by highlighting both the logistic advantages inherent in studies of the shared environment, as well as the use of nontraditional but still genetically informed research designs to study shared environmental influences. Although often moderate in magnitude prior to adulthood and free of unsystematic measurement error, shared environmental influences are nevertheless likely to have been underestimated in prior research. Moreover, the shared environment is likely to include proximal effects of the family, as well as the effects of more distal environmental contexts such as neighborhood and school. These risk and protective factors could influence the child either as main effects or as moderators of genetic influence (i.e. gene-environment interactions). Finally, because the absence of genetic relatedness in an otherwise nonindependent dataset also qualifies as 'genetically informed', studies of the shared environment are amenable to the use of novel and non-traditional designs (with appropriate controls for selection). The shared environment makes important contributions to most forms of child and adolescent psychopathology. Empirical examinations of the shared environment would thus be of real and critical value for understanding the development and persistence of common mental health issues prior to adulthood. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a Say?

PubMed Central

Zordan, Mauro Agostino; Sandrelli, Federica

2015-01-01

There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system leads to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here, we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e., a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia, and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease. PMID:25941512

Genetic and environmental influences on separation anxiety disorder symptoms and their moderation by age and sex.

PubMed

Feigon, S A; Waldman, I D; Levy, F; Hay, D A

2001-09-01

We estimated genetic and environmental influences on mother-rated DSM-III-R separation anxiety disorder (SAD) symptoms in 2043 3 to 18-year-old male and female twin pairs and their siblings (348 pairs) recruited from the Australian NH&MRC Twin Registry. Using DeFries and Fulker's (1985) multiple regression analysis, we found that genetic and shared environmental influences both contributed appreciably to variation in SAD symptoms (h2 = .47, SE = .07; c2 = .21, SE = .05) and were significantly moderated by both sex and age. Genetic influences were greater for girls than boys (h2 = .50 and .14, respectively), whereas shared environmental influences were greater for boys than girls (c2 = .51 and .21, respectively). Genetic influences increased with age. whereas shared environmental influences decreased with age. Shared environmental influences were greater in magnitude for twins than for nontwin siblings (c2 = .28 versus .13, respectively). Implications of these findings for theories of the cause of separation anxiety are discussed.

Sensation seeking and impulsive traits as personality endophenotypes for antisocial behavior: Evidence from two independent samples

PubMed Central

Mann, Frank D.; Engelhardt, Laura; Briley, Daniel A.; Grotzinger, Andrew D.; Patterson, Megan W.; Tackett, Jennifer L.; Strathan, Dixie B.; Heath, Andrew; Lynskey, Michael; Slutske, Wendy; Martin, Nicholas G.; Tucker-Drob, Elliot M.; Harden, K. Paige

2017-01-01

Sensation seeking and impulsivity are personality traits that are correlated with risk for antisocial behavior (ASB). This paper uses two independent samples of twins to (a) test the extent to which sensation seeking and impulsivity statistically mediate genetic influence on ASB, and (b) compare this to genetic influences accounted for by other personality traits. In Sample 1, delinquent behavior, as well as impulsivity, sensation seeking and Big Five personality traits, were measured in adolescent twins from the Texas Twin Project. In Sample 2, adult twins from the Australian Twin Registry responded to questionnaires that assessed individual differences in Eysenck's and Cloninger's personality dimensions, and a structured telephone interview that asked participants to retrospectively report DSM-defined symptoms of conduct disorder. Bivariate quantitative genetic models were used to identify genetic overlap between personality traits and ASB. Across both samples, novelty/sensation seeking and impulsive traits accounted for larger portions of genetic variance in ASB than other personality traits. We discuss whether sensation seeking and impulsive personality are causal endophenotypes for ASB, or merely index genetic liability for ASB. PMID:28824215

The genetic-environmental etiology of cognitive school readiness and later academic achievement in early childhood.

PubMed

Lemelin, Jean-Pascal; Boivin, Michel; Forget-Dubois, Nadine; Dionne, Ginette; Séguin, Jean R; Brendgen, Mara; Vitaro, Frank; Tremblay, Richard E; Pérusse, Daniel

2007-01-01

Using a genetic design of 840 60-month-old twins, this study investigated the genetic and environmental contributions to (a) individual differences in four components of cognitive school readiness, (b) the general ability underlying these four components, and (c) the predictive association between school readiness and school achievement. Results revealed that the contribution of the shared environment for cognitive school readiness was substantial. Genetic effects were more important for the core abilities underlying school readiness than for each specific skill, although shared environment remained the largest factor overall. Genetic, shared, and nonshared environmental factors all accounted for the predictive association between school readiness and early school achievement. These results contribute to a better understanding of the early determinants of school readiness.

Childhood separation anxiety disorder and adult onset panic attacks share a common genetic diathesis.

PubMed

Roberson-Nay, Roxann; Eaves, Lindon J; Hettema, John M; Kendler, Kenneth S; Silberg, Judy L

2012-04-01

Childhood separation anxiety disorder (SAD) is hypothesized to share etiologic roots with panic disorder. The aim of this study was to estimate the genetic and environmental sources of covariance between childhood SAD and adult onset panic attacks (AOPA), with the primary goal to determine whether these two phenotypes share a common genetic diathesis. Participants included parents and their monozygotic or dizygotic twins (n = 1,437 twin pairs) participating in the Virginia Twin Study of Adolescent Behavioral Development and those twins who later completed the Young Adult Follow-Up (YAFU). The Child and Adolescent Psychiatric Assessment was completed at three waves during childhood/adolescence followed by the Structured Clinical Interview for DSM-III-R at the YAFU. Two separate, bivariate Cholesky models were fit to childhood diagnoses of SAD and overanxious disorder (OAD), respectively, and their relation with AOPA; a trivariate Cholesky model also examined the collective influence of childhood SAD and OAD on AOPA. In the best-fitting bivariate model, the covariation between SAD and AOPA was accounted for by genetic and unique environmental factors only, with the genetic factor associated with childhood SAD explaining significant variance in AOPA. Environmental risk factors were not significantly shared between SAD and AOPA. By contrast, the genetic factor associated with childhood OAD did not contribute significantly to AOPA. Results of the trivariate Cholesky reaffirmed outcomes of bivariate models. These data indicate that childhood SAD and AOPA share a common genetic diathesis that is not observed for childhood OAD, strongly supporting the hypothesis of a specific genetic etiologic link between the two phenotypes. © 2012 Wiley Periodicals, Inc.

Choice of Reading Comprehension Test Influences the Outcomes of Genetic Analyses

PubMed Central

Betjemann, Rebecca S.; Keenan, Janice M.; Olson, Richard K.; DeFries, John C.

2010-01-01

Does the choice of test for assessing reading comprehension influence the outcome of genetic analyses? A twin design compared two types of reading comprehension tests classified as primarily associated with word decoding (RC-D) or listening comprehension (RC-LC). For both types of tests, the overall genetic influence is high and nearly identical. However, the tests differed significantly in how they covary with the genes associated with decoding and listening comprehension. Although Cholesky decomposition showed that both types of comprehension tests shared significant genetic influence with both decoding and listening comprehension, RC-D tests shared most genetic variance with decoding, and RC-LC tests shared most with listening comprehension. Thus, different tests used to measure the same construct may manifest very different patterns of genetic covariation. These results suggest that the apparent discrepancies among the findings of previous twin studies of reading comprehension could be due at least in part to test differences. PMID:21804757

Personality and language characteristics in parents from multiple-incidence autism families.

PubMed

Piven, J; Palmer, P; Landa, R; Santangelo, S; Jacobi, D; Childress, D

1997-07-25

Several studies have suggested that the genetic liability for autism may be expressed in non-autistic relatives of autistic probands, in behavioral characteristics that are milder but qualitatively similar to the defining features of autism. We employ a variety of direct assessment approaches to examine both personality and language in parents ascertained through having two autistic children (multiple-incidence autism parents) and parents of Down syndrome probands. Multiple-incidence autism parents had higher rates of particular personality characteristics (rigidity, aloofness, hypersensitivity to criticism, and anxiousness), speech and pragmatic language deficits, and more limited friendships than parents in the comparison group. The implications of these findings for future genetic studies of autism are discussed.

The Geography of Recent Genetic Ancestry across Europe

PubMed Central

Ralph, Peter; Coop, Graham

2013-01-01

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to conduct one of the first surveys of recent genealogical ancestry over the past 3,000 years at a continental scale. We detected 1.9 million shared long genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 2–12 genetic common ancestors from the last 1,500 years, and upwards of 100 genetic ancestors from the previous 1,000 years. These numbers drop off exponentially with geographic distance, but since these genetic ancestors are a tiny fraction of common genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1,000 years. There is also substantial regional variation in the number of shared genetic ancestors. For example, there are especially high numbers of common ancestors shared between many eastern populations that date roughly to the migration period (which includes the Slavic and Hunnic expansions into that region). Some of the lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of historical population expansions in these areas and/or more stably structured populations. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world. PMID:23667324

Genetic influences on heart rate variability

PubMed Central

Golosheykin, Simon; Grant, Julia D.; Novak, Olga V.; Heath, Andrew C.; Anokhin, Andrey P.

2016-01-01

Heart rate variability (HRV) is the variation of cardiac inter-beat intervals over time resulting largely from the interplay between the sympathetic and parasympathetic branches of the autonomic nervous system. Individual differences in HRV are associated with emotion regulation, personality, psychopathology, cardiovascular health, and mortality. Previous studies have shown significant heritability of HRV measures. Here we extend genetic research on HRV by investigating sex differences in genetic underpinnings of HRV, the degree of genetic overlap among different measurement domains of HRV, and phenotypic and genetic relationships between HRV and the resting heart rate (HR). We performed electrocardiogram (ECG) recordings in a large population-representative sample of young adult twins (n = 1060 individuals) and computed HRV measures from three domains: time, frequency, and nonlinear dynamics. Genetic and environmental influences on HRV measures were estimated using linear structural equation modeling of twin data. The results showed that variability of HRV and HR measures can be accounted for by additive genetic and non-shared environmental influences (AE model), with no evidence for significant shared environmental effects. Heritability estimates ranged from 47 to 64%, with little difference across HRV measurement domains. Genetic influences did not differ between genders for most variables except the square root of the mean squared differences between successive R-R intervals (RMSSD, higher heritability in males) and the ratio of low to high frequency power (LF/HF, distinct genetic factors operating in males and females). The results indicate high phenotypic and especially genetic correlations between HRV measures from different domains, suggesting that >90% of genetic influences are shared across measures. Finally, about 40% of genetic variance in HRV was shared with HR. In conclusion, both HR and HRV measures are highly heritable traits in the general population of young adults, with high degree of genetic overlap across different measurement domains. PMID:27114045

Psychopathic personality traits in 5 year old twins: the importance of genetic and shared environmental influences.

PubMed

Tuvblad, Catherine; Fanti, Kostas A; Andershed, Henrik; Colins, Olivier F; Larsson, Henrik

2017-04-01

There is limited research on the genetic and environmental bases of psychopathic personality traits in children. In this study, psychopathic personality traits were assessed in a total of 1189 5-year-old boys and girls drawn from the Preschool Twin Study in Sweden. Psychopathic personality traits were assessed with the Child Problematic Traits Inventory, a teacher-report measure of psychopathic personality traits in children ranging from 3 to 12 years old. Univariate results showed that genetic influences accounted for 57, 25, and 74 % of the variance in the grandiose-deceitful, callous-unemotional, and impulsive-need for stimulation dimensions, while the shared environment accounted for 17, 48 and 9 % (n.s.) in grandiose-deceitful and callous-unemotional, impulsive-need for stimulation dimensions, respectively. No sex differences were found in the genetic and environmental variance components. The non-shared environment accounted for the remaining 26, 27 and 17 % of the variance, respectively. The three dimensions of psychopathic personality were moderately correlated (0.54-0.66) and these correlations were primarily mediated by genetic and shared environmental factors. In contrast to research conducted with adolescent and adult twins, we found that both genetic and shared environmental factors influenced psychopathic personality traits in early childhood. These findings indicate that etiological models of psychopathic personality traits would benefit by taking developmental stages and processes into consideration.

Genetic relations among procrastination, impulsivity, and goal-management ability: implications for the evolutionary origin of procrastination.

PubMed

Gustavson, Daniel E; Miyake, Akira; Hewitt, John K; Friedman, Naomi P

2014-06-01

Previous research has revealed a moderate and positive correlation between procrastination and impulsivity. However, little is known about why these two constructs are related. In the present study, we used behavior-genetics methodology to test three predictions derived from an evolutionary account that postulates that procrastination arose as a by-product of impulsivity: (a) Procrastination is heritable, (b) the two traits share considerable genetic variation, and (c) goal-management ability is an important component of this shared variation. These predictions were confirmed. First, both procrastination and impulsivity were moderately heritable (46% and 49%, respectively). Second, although the two traits were separable at the phenotypic level (r = .65), they were not separable at the genetic level (r genetic = 1.0). Finally, variation in goal-management ability accounted for much of this shared genetic variation. These results suggest that procrastination and impulsivity are linked primarily through genetic influences on the ability to use high-priority goals to effectively regulate actions. © The Author(s) 2014.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics

PubMed Central

Evans, Barbara J

2014-01-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved—but still imperfect—framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics. Genet Med 16 7, 504–509. PMID:24357850

The Genetic and Environmental Sources of Resemblance Between Normative Personality and Personality Disorder Traits.

PubMed

Kendler, K S; Aggen, S H; Gillespie, Nathan; Neale, M C; Knudsen, G P; Krueger, R F; Czajkowski, Nikolai; Ystrom, Eivind; Reichborn-Kjennerud, T

2017-04-01

Recent work has suggested a high level of congruence between normative personality, most typically represented by the "big five" factors, and abnormal personality traits. In 2,293 Norwegian adult twins ascertained from a population-based registry, the authors evaluated the degree of sharing of genetic and environmental influences on normative personality, assessed by the Big Five Inventory (BFI), and personality disorder traits (PDTs), assessed by the Personality Inventory for DSM-5-Norwegian Brief Form (PID-5-NBF). For four of the five BFI dimensions, the strongest genetic correlation was observed with the expected PID-5-NBF dimension (e.g., neuroticism with negative affectivity [+], conscientiousness with disinhibition [-]). However, neuroticism, conscientiousness, and agreeableness had substantial genetic correlations with other PID-5-NBF dimensions (e.g., neuroticism with compulsivity [+], agreeableness with detachment [-]). Openness had no substantial genetic correlations with any PID-5-NBF dimension. The proportion of genetic risk factors shared in aggregate between the BFI traits and the PID-5-NBF dimensions was quite high for conscientiousness and neuroticism, relatively robust for extraversion and agreeableness, but quite low for openness. Of the six PID-5-NBF dimensions, three (negative affectivity, detachment, and disinhibition) shared, in aggregate, most of their genetic risk factors with normative personality traits. Genetic factors underlying psychoticism, antagonism, and compulsivity were shared to a lesser extent, suggesting that they are influenced by etiological factors not well indexed by the BFI.

Genetic and Environmental Influences on the Developmental Course of Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Adolescence.

PubMed

Pingault, Jean-Baptiste; Viding, Essi; Galéra, Cédric; Greven, Corina U; Zheng, Yao; Plomin, Robert; Rijsdijk, Frühling

2015-07-01

Attention-deficit/hyperactivity disorder (ADHD) is conceptualized as a neurodevelopmental disorder that is strongly heritable. However, to our knowledge, no study to date has examined the genetic and environmental influences explaining interindividual differences in the developmental course of ADHD symptoms from childhood to adolescence (ie, systematic decreases or increases with age). The reason ADHD symptoms persist in some children but decline in others is an important concern, with implications for prognosis and interventions. To assess the proportional impact of genes and the environment on interindividual differences in the developmental course of ADHD symptom domains of hyperactivity/impulsivity and inattention between ages 8 and 16 years. A prospective sample of 8395 twin pairs from the Twins Early Development Study, recruited from population records of births in England and Wales between January 1, 1994, and December 31, 1996. Data collection at age 8 years took place between November 2002 and November 2004; data collection at age 16 years took place between February 2011 and January 2013. Both DSM-IV ADHD symptom subscales were rated 4 times by participants' mothers. Estimates from latent growth curve models indicated that the developmental course of hyperactivity/impulsivity symptoms followed a sharp linear decrease (mean score of 6.0 at age 8 years to 2.9 at age 16 years). Interindividual differences in the linear change in hyperactivity/impulsivity were under strong additive genetic influences (81%; 95% CI, 73%-88%). More than half of the genetic variation was specific to the developmental course and not shared with the baseline level of hyperactivity/impulsivity. The linear decrease in inattention symptoms was less pronounced (mean score of 5.8 at age 8 years to 4.9 at age 16 years). Nonadditive genetic influences accounted for a substantial amount of variation in the developmental course of inattention symptoms (54%; 95% CI, 8%-76%), with more than half being specific to the developmental course. The large genetic influences on the developmental course of ADHD symptoms are mostly specific and independent of those that account for variation in the baseline level of symptoms. Different sets of genes may be associated with the developmental course vs the baseline level of ADHD symptoms and explain why some children remit from ADHD, whereas others persist. Recent longitudinal imaging data indicate that the maintenance or increase in symptoms is underpinned by atypical trajectories of cortical development. This may reflect a specific genetic liability, distinct from that which contributes to baseline ADHD symptoms, and warrants closer follow-up.

Remedying CERCLA`s natural resource damages provision: Incorporation of the public trust doctrine into natural resource damage actions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chase, A.R.

When Congress enacted the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), it ushered in a sweeping approach to controlling the environmental effects of improper hazardous waste disposal. CERCLA`s cleanup provisions, which focus on removal and remediation of hazardous substances from inactive hazardous waste sites, have progressed through more than a decade of litigation and a great deal of public debate. However, CERCLA`s natural resource damage provisions have not shared this same degree of progress.

Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts.

PubMed

Kawamoto, Kensaku; Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

2013-01-01

To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care.

Neurological soft signs in first-episode schizophrenia: a follow-up study.

PubMed

Bachmann, Silke; Bottmer, Christina; Schröder, Johannes

2005-12-01

Neurological soft signs are frequently found in schizophrenia. They are indicators of both genetic liability and psychopathological symptoms. To further differentiate "trait" and "state" relations the authors compared the 1-year course of neurological soft signs in schizophrenia patients and comparison subjects. Thirty-nine patients with first-episode schizophrenia spectrum disorders were examined after remission of acute symptoms and 14 months later. Established instruments assessed diagnoses, psychopathological symptoms, predictors of outcome, handedness, and neurological soft signs. Twenty-two age- and gender-matched comparison subjects were also examined twice. Neurological soft sign scores in patients were significantly elevated relative to comparison subjects at both measurement points. Whereas neurological soft signs remained stable in comparison subjects (time 1: mean=4.8, SD=3.3; time 2: mean=4.6, SD=3.9), they significantly decreased in patients (time 1: mean=15.7, SD=7.1; time 2: mean=10.1, SD=7.9). This effect was more pronounced in patients with a favorable versus a chronic course and was mainly accounted for by motor signs. Predictors of follow-up neurological soft sign scores were neurological soft sign levels at remission and compliance with treatment. Although neurological soft signs are intrinsic to schizophrenia, their level varies with the clinical course. Thus, neurological soft signs may correspond to both genetic liability and the activity of the disease process and may be considered as potential predictors of outcome.

Clinical, electrophysiological, genetic, and imaging features of six Chinese Han patients with hereditary neuropathy with liability to pressure palsies (HNPP).

PubMed

Chen, Bin; Niu, Songtao; Wang, Xingao; Li, Wei; Chen, Na; Zhang, Zaiqiang

2018-02-01

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. This study summarizes the clinical, electrophysiological, genetic, and imaging features of six unrelated Chinese Han patients with HNPP. Age of onset was within the second decade in five patients, and 46 years of age in one patient. Weakness or numbness in a unilateral lower extremity was the most common symptom in 5 patients, and bilateral sensorineural hearing loss was also detected in one patient. Electrophysiological presentations suggested demyelinating sensory-motor polyneuropathy in the group. Magnetic resonance imaging (MRI) of the cervical and lumbar spine revealed varying degrees of degeneration in five patients, and mild kyphosis of cervical vertebral bodies in 2 teen-aged patients. In addition, cranial MRI of one patient showed scattered demyelination in the frontal lobes. Targeted next-generation-sequencing (NGS) revealed a PMP22 deletion in five patients and a heterozygous c.199G>A mutation in exon 4 of PMP22 in one patient. The I92V variant of lipopolysaccharide-induced tumor necrosis factor (LITAF) gene was found in one patient. There was no relationship between the Ile92Val variant of LITAF and age of onset in this group, albeit the sample size was very small. Copyright © 2017 Elsevier Ltd. All rights reserved.

Testing positive for a genetic predisposition to depression magnifies retrospective memory for depressive symptoms.

PubMed

Lebowitz, Matthew S; Ahn, Woo-Kyoung

2017-11-01

Depression, like other mental disorders and health conditions generally, is increasingly construed as genetically based. This research sought to determine whether merely telling people that they have a genetic predisposition to depression can cause them to retroactively remember having experienced it. U.S. adults (men and women) were recruited online to participate (Experiment 1: N = 288; Experiment 2: N = 599). After conducting a test disguised as genetic screening, we randomly assigned some participants to be told that they carried elevated genetic susceptibility to depression, whereas others were told that they did not carry this genetic liability or were told that they carried elevated susceptibility to a different disorder. Participants then rated their experience of depressive symptoms over the prior 2 weeks on a modified version of the Beck Depression Inventory-II. Participants who were told that their genes predisposed them to depression generally reported higher levels of depressive symptomatology over the previous 2 weeks, compared to those who did not receive this feedback. Given the central role of self-report in psychiatric diagnosis, these findings highlight potentially harmful consequences of personalized genetic testing in mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Personality traits of the relatives of autistic probands.

PubMed

Murphy, M; Bolton, P F; Pickles, A; Fombonne, E; Piven, J; Rutter, M

2000-11-01

There is substantial evidence that the genetic liability to autism confers a risk for a range of more subtle social and communication impairments, as well as stereotyped and repetitive behaviours. Recent research suggests that increased expression of particular personality traits may be a manifestation of the liability to autism. To investigate this we examined the personality traits of the adult relatives of 99 autistic and 36 Down's syndrome probands, using the informant version of the Modified Personality Assessment Schedule. There was significantly increased expression of the traits anxious, impulsive, aloof, shy, over-sensitive, irritable and eccentric among the autism relatives with evidence of different profiles for male and female relatives and for parents and adult children. Factor analysis revealed three broad groups of traits, two of which ('withdrawn' and 'difficult') appeared to reflect impairments in social functioning and a third group of anxiety related traits ('tense'). Each of these factors differed in their pattern of associations with the factor we termed 'withdrawn' showing a similar pattern of association to that found for other autism related conditions. The 'tense' factor appeared in part to be related to the burden of caring for an autistic child. This study confirms the finding that particular personality traits may aggregate in the family members of autistic individuals and furthermore that some of these traits may be a manifestation of the liability to autism.

Quasi-causal associations of physical activity and neighborhood walkability with body mass index: a twin study.

PubMed

Duncan, Glen E; Cash, Stephanie Whisnant; Horn, Erin E; Turkheimer, Eric

2015-01-01

Physical activity, neighborhood walkability, and body mass index (BMI, kg/m(2)) associations were tested using quasi-experimental twin methods. We hypothesized that physical activity and walkability were independently associated with BMI within twin pairs, controlling for genetic and environmental background shared between them. Data were from 6376 (64% female; 58% identical) same-sex pairs, University of Washington Twin Registry, 2008-2013. Neighborhood walking, moderate-to-vigorous physical activity (MVPA), and BMI were self-reported. Residential address was used to calculate walkability. Phenotypic (non-genetically informed) and biometric (genetically informed) regression was employed, controlling for age, sex, and race. Walking and MVPA were associated with BMI in phenotypic analyses; associations were attenuated but significant in biometric analyses (Ps<0.05). Walkability was not associated with BMI, however, was associated with walking (but not MVPA) in both phenotypic and biometric analyses (Ps<0.05), with no attenuation accounting for shared genetic and environmental background. The association between activity and BMI is largely due to shared genetic and environmental factors, but a significant causal relationship remains accounting for shared background. Although walkability is not associated with BMI, it is associated with neighborhood walking (but not MVPA) accounting for shared background, suggesting a causal relationship between them. Copyright © 2014 Elsevier Inc. All rights reserved.

Shared Environment Estimates for Educational Attainment: A Puzzle and Possible Solutions.

PubMed

Freese, Jeremy; Jao, Yu-Han

2017-02-01

Classical behavioral genetics models for twin and other family designs decompose traits into heritability, shared environment, and nonshared environment components. Estimates of heritability of adult traits are pervasively observed to be far higher than those of shared environment, which has been used to make broad claims about the impotence of upbringing. However, the most commonly studied nondemographic variable in many areas of social science, educational attainment, exhibits robustly high estimates both for heritability and for shared environment. When previously noticed, the usual explanation has emphasized family resources, but evidence suggests this is unlikely to explain the anomalous high estimates for shared environment of educational attainment. We articulate eight potential complementary explanations and discuss evidence of their prospective contributions to resolving the puzzle. In so doing, we hope to further consideration of how behavioral genetics findings may advance studies of social stratification beyond the effort to articulate specific genetic influences. © 2015 Wiley Periodicals, Inc.

A data-driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome-wide significant genetic loci.

PubMed

Leonenko, Ganna; Di Florio, Arianna; Allardyce, Judith; Forty, Liz; Knott, Sarah; Jones, Lisa; Gordon-Smith, Katherine; Owen, Michael J; Jones, Ian; Walters, James; Craddock, Nick; O'Donovan, Michael C; Escott-Price, Valentina

2018-06-01

The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk alleles, many of which are shared across the disorders. BD is clinically heterogeneous and it has been postulated that the pattern of symptoms is in part determined by the particular risk alleles carried, and in particular, that risk alleles also confer liability to schizophrenia influence psychotic symptoms in those with BD. To investigate links between psychotic symptoms in BD and schizophrenia risk alleles we employed a data-driven approach in a genotyped and deeply phenotyped sample of subjects with BD. We used sparse canonical correlation analysis (sCCA) (Witten, Tibshirani, & Hastie, ) to analyze 30 psychotic symptoms, assessed with the OPerational CRITeria checklist, and 82 independent genome-wide significant single nucleotide polymorphisms (SNPs) identified by the Schizophrenia Working group of the Psychiatric Genomics Consortium for which we had data in our BD sample (3,903 subjects). As a secondary analysis, we applied sCCA to larger groups of SNPs, and also to groups of symptoms defined according to a published factor analyses of schizophrenia. sCCA analysis based on individual psychotic symptoms revealed a significant association (p = .033), with the largest weights attributed to a variant on chromosome 3 (rs11411529), chr3:180594593, build 37) and delusions of influence, bizarre behavior and grandiose delusions. sCCA analysis using the same set of SNPs supported association with the same SNP and the group of symptoms defined "factor 3" (p = .012). A significant association was also observed to the "factor 3" phenotype group when we included a greater number of SNPs that were less stringently associated with schizophrenia; although other SNPs contributed to the significant multivariate association result, the greatest weight remained assigned to rs11411529. Our results suggest that the canonical correlation is a useful tool to explore phenotype-genotype relationships. To the best of our knowledge, this is the first study to apply this approach to complex, polygenic psychiatric traits. The sparse canonical correlation approach offers the potential to include a larger number of fine-grained systematic descriptors, and to include genetic markers associated with other disorders that are genetically correlated with BD. © 2018 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

A patient with PMP22-related hereditary neuropathy and DBH-gene-related dysautonomia.

PubMed

Bartoletti-Stella, Anna; Chiaro, Giacomo; Calandra-Buonaura, Giovanna; Contin, Manuela; Scaglione, Cesa; Barletta, Giorgio; Cecere, Annagrazia; Garagnani, Paolo; Tieri, Paolo; Ferrarini, Alberto; Piras, Silvia; Franceschi, Claudio; Delledonne, Massimo; Cortelli, Pietro; Capellari, Sabina

2015-10-01

Recurrent focal neuropathy with liability to pressure palsies is a relatively frequent autosomal-dominant demyelinating neuropathy linked to peripheral myelin protein 22 (PMP22) gene deletions. The combination of PMP22 gene mutations with other genetic variants is known to cause a more severe phenotype than expected. We present the case of a patient with severe orthostatic hypotension since 12 years of age, who inherited a PMP22 gene deletion from his father. Genetic double trouble was suspected because of selective sympathetic autonomic disturbances. Through exome-sequencing analysis, we identified two novel mutations in the dopamine beta hydroxylase gene. Moreover, with interactome analysis, we excluded a further influence on the origin of the disease by variants in other genes. This case increases the number of unique patients presenting with dopamine-β-hydroxylase deficiency and of cases with genetically proven double trouble. Finding the right, complete diagnosis is crucial to obtain adequate medical care and appropriate genetic counseling.

Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.

PubMed

Smit, Dirk J A; Wright, Margaret J; Meyers, Jacquelyn L; Martin, Nicholas G; Ho, Yvonne Y W; Malone, Stephen M; Zhang, Jian; Burwell, Scott J; Chorlian, David B; de Geus, Eco J C; Denys, Damiaan; Hansell, Narelle K; Hottenga, Jouke-Jan; McGue, Matt; van Beijsterveldt, Catharina E M; Jahanshad, Neda; Thompson, Paul M; Whelan, Christopher D; Medland, Sarah E; Porjesz, Bernice; Lacono, William G; Boomsma, Dorret I

2018-06-26

Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but current understanding of specific genetic influences remains limited. We performed the largest genome-wide association study to date of oscillatory power during eyes-closed resting electroencephalogram (EEG) across a range of frequencies (delta 1-3.75 Hz, theta 4-7.75 Hz, alpha 8-12.75 Hz, and beta 13-30 Hz) in 8,425 subjects. Additionally, we performed KGG positional gene-based analysis and brain-expression analyses. GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly affected beta power, consistent with the known relation between GABA A interneuron activity and beta oscillations. Tissue-specific SNP-based imputation of gene-expression levels based on the GTEx database revealed that hippocampal GABRA2 expression may mediate this effect. Twenty-four genes at 3p21.1 were significant for alpha power (FDR q < .05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex-genes that were previously implicated in schizophrenia and bipolar disorder. In sum, we identified several novel genetic variants associated with oscillatory brain activity; furthermore, we replicated and advanced understanding of previously known genes associated with psychopathology (i.e., schizophrenia and alcohol use disorders). Importantly, these psychopathological liability genes affect brain functioning, linking the genes' expression to specific cortical/subcortical brain regions. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Hereditary neuropathy with liability to pressure palsy: a brief review with a case report.

PubMed

Rana, Abdul Qayyum; Masroor, Mohamed Sufian

2012-03-01

Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is an autosomal dominant disorder and is usually characterized by episodes of recurrent and painless focal motor and sensory peripheral mononeuropathy. This condition is usually localized around areas of entrapment (predominantly the wrists, knees, elbows, and shoulders). The genetic locus of the disease is chromosome 17p12. A deletion of the PMP22 gene results in the lack of peripheral myelin protein, a key component to the myelin sheet of peripheral nerves. However, this disease may be completely asymptomatic until an event, such as a minor trauma, triggers these episodes, as seen in our presented case report. The diagnosis of HNPP can be somewhat challenging, as other diseases, such as Charcot-Marie-Tooth disease type 1A (CMT) and Hereditary Neuralgic Amyotrophy (HNA) must be included in the differential diagnosis due to their overlapping clinical features. There are currently no treatments to cure the disease, but therapies seek to alleviate the symptoms and recurring episodes.

Sociocultural definitions of risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rayner, S.

1990-10-01

Public constituencies frequently are criticized by technical experts as being irrational in response to low-probability risks. This presentation argued that most people are concerned with a variety of risk attributes other than probability and that is rather irrational to exclude these from the definition and analysis of technological risk. Risk communication, which is at the heart of the right-to-know concept, is described as the creation of shared meaning rather than the mere transmission of information. A case study of utilities, public utility commissions, and public interest groups illustrates how the diversity of institutional cultures in modern society leads to problemsmore » for the creation of shared meanings in establishing trust, distributing liability, and obtaining consent to risk. This holistic approach to risk analysis is most appropriate under conditions of high uncertainty and/or decision stakes. 1 fig., 5 tabs.« less

Legal semantics. Nurses and non-surgical abortions.

PubMed

Rae, K

1981-02-26

A 1980 law was confirmed by the House of Lords majority which allows nurses to participate in the nonsurgical prostaglandin termination of pregnancy. Nurses are acting under written instructions of a doctor when carrying out the procedure, although they also terminate the pregnancy. A nurse is now in danger of liability litigation if she fails at any stage of the termination to perform successfully. The majority decision made the two words "termination" and "treatment" of pregnancy synonymous. Nurses are to act in a ministerial capacity and on doctors' orders. Doctors are to share in any liability if negligence should occur. The question remains: will they? The procedure includes the following: attachment of the catheter to the prostaglandin pump; switching on of pump; insertion of a cannula into the vein; attachment and commencement of the oxytocin intravenous infusion; monitoring of the patient's observations; adjustment of the flow rates of both infusions; and, discontinuation of the process once the fetus is discharged or a fixed period has expired after which the operation is considered to have failed (usually 30 hours).

Shared Genetic Architecture in the Relationship between Adult Stature and Subclinical Coronary Artery Atherosclerosis

PubMed Central

Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Sheedy, Patrick F.; Turner, Stephen T.; Chu, Julia S.; Peyser, Patricia A.

2011-01-01

Background Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. Methods 877 asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Results Adult height was significantly and inversely associated with CAC score (P=0.01). After adjusting for age, sex, and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P=0.001) and -1 (P<0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P=0.024). Conclusions Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. PMID:21937044

Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis.

PubMed

Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy, Patrick F; Turner, Stephen T; Chu, Julia S; Peyser, Patricia A

2011-12-01

Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. 877 Asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Adult height was significantly and inversely associated with CAC score (P = 0.01). After adjusting for age, sex and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P = 0.001) and -1 (P < 0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P = 0.024). Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Canadian Open Genetics Repository (COGR): a unified clinical genomics database as a community resource for standardising and sharing genetic interpretations.

PubMed

Lerner-Ellis, Jordan; Wang, Marina; White, Shana; Lebo, Matthew S

2015-07-01

The Canadian Open Genetics Repository is a collaborative effort for the collection, storage, sharing and robust analysis of variants reported by medical diagnostics laboratories across Canada. As clinical laboratories adopt modern genomics technologies, the need for this type of collaborative framework is increasingly important. A survey to assess existing protocols for variant classification and reporting was delivered to clinical genetics laboratories across Canada. Based on feedback from this survey, a variant assessment tool was made available to all laboratories. Each participating laboratory was provided with an instance of GeneInsight, a software featuring versioning and approval processes for variant assessments and interpretations and allowing for variant data to be shared between instances. Guidelines were established for sharing data among clinical laboratories and in the final outreach phase, data will be made readily available to patient advocacy groups for general use. The survey demonstrated the need for improved standardisation and data sharing across the country. A variant assessment template was made available to the community to aid with standardisation. Instances of the GeneInsight tool were provided to clinical diagnostic laboratories across Canada for the purpose of uploading, transferring, accessing and sharing variant data. As an ongoing endeavour and a permanent resource, the Canadian Open Genetics Repository aims to serve as a focal point for the collaboration of Canadian laboratories with other countries in the development of tools that take full advantage of laboratory data in diagnosing, managing and treating genetic diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[The genetics of depressive disorders].

PubMed

Schulte-Körne, Gerd; Allgaier, Antje-Kathrin

2008-01-01

Among the most common severe psychiatric disorders worldwide, depressive disorders are a leading cause of morbidity, the onset usually occurring during childhood or adolescence. Symptomatology, prevalence, outcome and treatment differentiate depressive disorder nosologically as being either unipolar depression or bipolar disorder, which is characterized by one or more episodes of mania with or without episodes of depression. Genetic factors decisively influence the susceptibility to depressive disorders. Family studies and twin studies have been essential in defining the magnitude of familial risk and liability to heritability, particularly in the case of bipolar disorder. In recent years, linkage and association studies have made great strides towards identifying candidate genes. Particularly the s-allele of the serotonin transporter has been repeatedly confirmed to be a risk factor. Meta-analyses suggest, however, that the genetic contributions of the ascertained loci are relatively small. Along with genetic factors, environmental factors are heavily involved. Gene-environment action plays a pivotal role, particularly in unipolar depression. The genetic disposition seems to be modulated by a protective or pathogenic environment. Early-onset disorders must be further investigated in future as studies to date are somewhat limited.

Genetic and environmental contributions to the associations between intraindividual variability in reaction time and cognitive function.

PubMed

Finkel, Deborah; Pedersen, Nancy L

2014-01-01

Intraindividual variability (IIV) in reaction time has been related to cognitive decline, but questions remain about the nature of this relationship. Mean and range in movement and decision time for simple reaction time were available from 241 individuals aged 51-86 years at the fifth testing wave of the Swedish Adoption/Twin Study of Aging. Cognitive performance on four factors was also available: verbal, spatial, memory, and speed. Analyses indicated that range in reaction time could be used as an indicator of IIV. Heritability estimates were 35% for mean reaction and 20% for range in reaction. Multivariate analysis indicated that the genetic variance on the memory, speed, and spatial factors is shared with genetic variance for mean or range in reaction time. IIV shares significant genetic variance with fluid ability in late adulthood, over and above and genetic variance shared with mean reaction time.

Experiences of college-age youths in families with a recessive genetic condition.

PubMed

Hern, Marcia J; Beery, Theresa A; Barry, Detrice G

2006-05-01

Growing up in a family with a recessive genetic condition can trigger questions about progeny effect. This study explored perceptions of family hardiness and information sharing by 18- to 21-year-olds about genetic risk. Semistructured interviews, the Family Hardiness Index (FHI), and a Family Information Sharing Analog Scale (FISAS) were used. Participants included 11 youths who had relatives with hemophilia and 4 with sickle cell anemia. Findings revealed seven themes: assimilating premature knowledge; caring for others, denying self; cautioning during development; experiencing continual sickness; feeling less than; magnifying transition experiences; and sustaining by faith. There was no significant correlation between total FHI and FISAS. However, there was a statistically significant difference in FISAS between genetic condition variance. Specifically, higher hardiness was found and information sharing correlated among college youths in families with hemophilia. Additional research can lead to nursing interventions to provide genetic information to youths in families for illness variance.

Genetic Relations Among Procrastination, Impulsivity, and Goal-Management Ability: Implications for the Evolutionary Origin of Procrastination

PubMed Central

Gustavson, Daniel E.; Miyake, Akira; Hewitt, John K.; Friedman, Naomi P.

2014-01-01

Previous research has revealed a moderate positive correlation between procrastination and impulsivity. However, little is known about why these two constructs are related. This study used behavioral genetic methodology to test three predictions derived from an evolutionary account that postulates that procrastination arose as a by-product of impulsivity (Steel, 2010): (a) Procrastination is heritable; (b) the two traits share considerable genetic variation; and (c) goal-management ability is an important component of this shared variation. These predictions were confirmed. First, both procrastination and impulsivity were moderately heritable (46% and 49%, respectively). Second, although the two traits were separable at the phenotypic level (r=.65), they were not separable at the genetic level (rg=1.0). Finally, variation in goal-management ability accounted for much of this shared genetic variation. These results suggest that procrastination and impulsivity are linked primarily through genetic influences on the ability to use their high-priority goals effectively to regulate their action. PMID:24705635

Strain-dependent Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

PubMed Central

Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen

2013-01-01

The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute nicotine and nicotine withdrawal on contextual fear conditioning, somatic signs, and the elevated plus maze were observed, but no association between the effects of acute nicotine and nicotine withdrawal on contextual fear conditioning were observed, suggesting that different genetic substrates may mediate these effects. The identification of genetic factors that may alter the effects of nicotine on cognition may lead to more efficacious treatments for nicotine addiction. PMID:21822688

Some legal aspects of genetic screening.

PubMed

Abbing, H R

2003-01-01

Screening activities in health care are not always useful and sometimes harmful. The mere offer of a screening test puts the individual's autonomy under constraint. With genetic (predictive and risk assessment) tests, the right to free, informed consent and to protection of privacy and medical confidentiality is even more warranted. Screening evokes many questions from the perspective of the right to health care as well as (in particular with genetic screening) from the perspective of respect for individual human rights. Fear of liability puts pressure on professional restraint not to offer every screening test available. States have to take legislative measures for guaranteeing that only those screening activities become available that can significantly contribute to individual and public health. They also should consider additional rules for protecting individual rights where those that are generally accepted in the "ordinary" medical setting (the individual patient-doctor relationship), offer insufficient protection.

Genetic covariance between components of male reproductive success: within-pair vs. extra-pair paternity in song sparrows

PubMed Central

Reid, J M; Arcese, P; Losdat, S

2014-01-01

The evolutionary trajectories of reproductive systems, including both male and female multiple mating and hence polygyny and polyandry, are expected to depend on the additive genetic variances and covariances in and among components of male reproductive success achieved through different reproductive tactics. However, genetic covariances among key components of male reproductive success have not been estimated in wild populations. We used comprehensive paternity data from socially monogamous but genetically polygynandrous song sparrows (Melospiza melodia) to estimate additive genetic variance and covariance in the total number of offspring a male sired per year outside his social pairings (i.e. his total extra-pair reproductive success achieved through multiple mating) and his liability to sire offspring produced by his socially paired female (i.e. his success in defending within-pair paternity). Both components of male fitness showed nonzero additive genetic variance, and the estimated genetic covariance was positive, implying that males with high additive genetic value for extra-pair reproduction also have high additive genetic propensity to sire their socially paired female's offspring. There was consequently no evidence of a genetic or phenotypic trade-off between male within-pair paternity success and extra-pair reproductive success. Such positive genetic covariance might be expected to facilitate ongoing evolution of polygyny and could also shape the ongoing evolution of polyandry through indirect selection. PMID:25186454

Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population

PubMed Central

Yin, Xianyong; Wineinger, Nathan E.; Wang, Kai; Yue, Weihua; Norgren, Nina; Wang, Ling; Yao, Weiyi; Jiang, Xiaoyun; Wu, Bo; Cui, Yong; Shen, Changbing; Cheng, Hui; Zhou, Fusheng; Chen, Gang; Zuo, Xianbo; Zheng, Xiaodong; Fan, Xing; Wang, Hongyan; Wang, Lifang; Lee, Jimmy; Lam, Max; Tai, E. Shyong; Zhang, Zheng; Huang, Qiong; Sun, Liangdan; Xu, Jinhua; Yang, Sen; Wilhelmsen, Kirk C.; Liu, Jianjun; Schork, Nicholas J.; Zhang, Xuejun

2016-01-01

Background Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10−8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10−16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways. PMID:27091718

Temperament and Character in the Child and Adolescent Twin Study in Sweden (CATSS): Comparison to the General Population, and Genetic Structure Analysis

PubMed Central

Garcia, Danilo; Lundström, Sebastian; Brändström, Sven; Råstam, Maria; Cloninger, C. Robert; Kerekes, Nóra; Nilsson, Thomas; Anckarsäter, Henrik

2013-01-01

Background The Child and Adolescent Twin Study in Sweden (CATSS) is an on-going, large population-based longitudinal twin study. We aimed (1) to investigate the reliability of two different versions (125-items and 238-items) of Cloninger's Temperament and Character Inventory (TCI) used in the CATSS and the validity of extracting the short version from the long version, (2) to compare these personality dimensions between twins and adolescents from the general population, and (3) to investigate the genetic structure of Cloninger's model. Method Reliability and correlation analyses were conducted for both TCI versions, 2,714 CATSS-twins were compared to 631 adolescents from the general population, and the genetic structure was investigated through univariate genetic analyses, using a model-fitting approach with structural equation-modeling techniques based on same-sex twin pairs from the CATSS (423 monozygotic and 408 dizygotic pairs). Results The TCI scores from the short and long versions showed comparable reliability coefficients and were strongly correlated. Twins scored about half a standard deviation higher in the character scales. Three of the four temperament dimensions (Novelty Seeking, Harm Avoidance, and Persistence) had strong genetic and non-shared environmental effects, while Reward Dependence and the three character dimensions had moderate genetic effects, and both shared and non-shared environmental effects. Conclusions Twins showed higher scores in character dimensions compared to adolescents from the general population. At least among adolescents there is a shared environmental influence for all of the character dimensions, but only for one of the temperament dimensions (i.e., Reward Dependence). This specific finding regarding the existence of shared environmental factors behind the character dimensions in adolescence, together with earlier findings showing a small shared environmental effects on character among young adults and no shared environmental effects on character among adults, suggest that there is a shift in type of environmental influence from adolescence to adulthood regarding character. PMID:23940581

The prosocial personality and its facets: genetic and environmental architecture of mother-reported behavior of 7-year-old twins

PubMed Central

Knafo-Noam, Ariel; Uzefovsky, Florina; Israel, Salomon; Davidov, Maayan; Zahn-Waxler, Caroyln

2015-01-01

Children vary markedly in their tendency to behave prosocially, and recent research has implicated both genetic and environmental factors in this variability. Yet, little is known about the extent to which different aspects of prosociality constitute a single dimension (the prosocial personality), and to the extent they are intercorrelated, whether these aspects share their genetic and environmental origins. As part of the Longitudinal Israeli Study of Twins (LIST), mothers of 183 monozygotic (MZ) and dizygotic (DZ) 7-year-old twin pairs (51.6% male) reported regarding their children’s prosociality using questionnaires. Five prosociality facets (sharing, social concern, kindness, helping, and empathic concern) were identified. All five facets intercorrelated positively (r > 0.39) suggesting a single-factor structure to the data, consistent with the theoretical idea of a single prosociality trait. Higher MZ than DZ twin correlations indicated genetic contributions to each prosociality facet. A common-factor-common-pathway multivariate model estimated high (69%) heritability for the common prosociality factor, with the non-shared environment and error accounting for the remaining variance. For each facet, unique genetic and environmental contributions were identified as well. The results point to the presence of a broad prosociality phenotype, largely affected by genetics; whereas additional genetic and environmental factors contribute to different aspects of prosociality, such as helping and sharing. PMID:25762952

The ABCs of Math: A Genetic Analysis of Mathematics and Its Links With Reading Ability and General Cognitive Ability

PubMed Central

Hart, Sara A.; Petrill, Stephen A.; Thompson, Lee A.; Plomin, Robert

2009-01-01

The goal of this first major report from the Western Reserve Reading Project Math component is to explore the etiology of the relationship among tester-administered measures of mathematics ability, reading ability, and general cognitive ability. Data are available on 314 pairs of monozygotic and same-sex dizygotic twins analyzed across 5 waves of assessment. Univariate analyses provide a range of estimates of genetic (h2 = .00 –.63) and shared (c2 = .15–.52) environmental influences across math calculation, fluency, and problem solving measures. Multivariate analyses indicate genetic overlap between math problem solving with general cognitive ability and reading decoding, whereas math fluency shares significant genetic overlap with reading fluency and general cognitive ability. Further, math fluency has unique genetic influences. In general, math ability has shared environmental overlap with general cognitive ability and decoding. These results indicate that aspects of math that include problem solving have different genetic and environmental influences than math calculation. Moreover, math fluency, a timed measure of calculation, is the only measured math ability with unique genetic influences. PMID:20157630

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

PubMed

Evans, Barbara J

2014-07-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

Causes of individual differences in adolescent optimism: a study in Dutch twins and their siblings.

PubMed

Mavioğlu, Rezan Nehir; Boomsma, Dorret I; Bartels, Meike

2015-11-01

The aim of this study was to investigate the degree to which genetic and environmental influences affect variation in adolescent optimism. Optimism (3 items and 6 items approach) and pessimism were assessed by the Life Orientation Test-Revised (LOT-R) in 5,187 adolescent twins and 999 of their non-twin siblings from the Netherlands Twin Register (NTR). Males reported significantly higher optimism scores than females, while females score higher on pessimism. Genetic structural equation modeling revealed that about one-third of the variance in optimism and pessimism was due to additive genetic effects, with the remaining variance being explained by non-shared environmental effects. A bivariate correlated factor model revealed two dimensions with a genetic correlation of -.57 (CI -.67, -.47), while the non-shared environmental correlation was estimated to be -.21 (CI -.25, -.16). Neither an effect of shared environment, non-additive genetic influences, nor quantitative sex differences was found for both dimensions. This result indicates that individual differences in adolescent optimism are mainly accounted for by non-shared environmental factors. These environmental factors do not contribute to the similarity of family members, but to differences between them. Familial resemblance in optimism and pessimism assessed in adolescents is fully accounted for by genetic overlap between family members.

Model invariance across genders of the Broad Autism Phenotype Questionnaire.

PubMed

Broderick, Neill; Wade, Jordan L; Meyer, J Patrick; Hull, Michael; Reeve, Ronald E

2015-10-01

ASD is one of the most heritable neuropsychiatric disorders, though comprehensive genetic liability remains elusive. To facilitate genetic research, researchers employ the concept of the broad autism phenotype (BAP), a milder presentation of traits in undiagnosed relatives. Research suggests that the BAP Questionnaire (BAPQ) demonstrates psychometric properties superior to other self-report measures. To examine evidence regarding validity of the BAPQ, the current study used confirmatory factor analysis to test the assumption of model invariance across genders. Results of the current study upheld model invariance at each level of parameter constraint; however, model fit indices suggested limited goodness-of-fit between the proposed model and the sample. Exploratory analyses investigated alternate factor structure models but ultimately supported the proposed three-factor structure model.

DNA Methylation in Schizophrenia.

PubMed

Pries, Lotta-Katrin; Gülöksüz, Sinan; Kenis, Gunter

2017-01-01

Schizophrenia is a highly heritable psychiatric condition that displays a complex phenotype. A multitude of genetic susceptibility loci have now been identified, but these fail to explain the high heritability estimates of schizophrenia. In addition, epidemiologically relevant environmental risk factors for schizophrenia may lead to permanent changes in brain function. In conjunction with genetic liability, these environmental risk factors-likely through epigenetic mechanisms-may give rise to schizophrenia, a clinical syndrome characterized by florid psychotic symptoms and moderate to severe cognitive impairment. These pathophysiological features point to the involvement of epigenetic processes. Recently, a wave of studies examining aberrant DNA modifications in schizophrenia was published. This chapter aims to comprehensively review the current findings, from both candidate gene studies and genome-wide approaches, on DNA methylation changes in schizophrenia.

Pervasive sharing of genetic effects in autoimmune disease.

PubMed

Cotsapas, Chris; Voight, Benjamin F; Rossin, Elizabeth; Lage, Kasper; Neale, Benjamin M; Wallace, Chris; Abecasis, Gonçalo R; Barrett, Jeffrey C; Behrens, Timothy; Cho, Judy; De Jager, Philip L; Elder, James T; Graham, Robert R; Gregersen, Peter; Klareskog, Lars; Siminovitch, Katherine A; van Heel, David A; Wijmenga, Cisca; Worthington, Jane; Todd, John A; Hafler, David A; Rich, Stephen S; Daly, Mark J

2011-08-01

Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.

The intergenerational correlation in weight: How genetic resemblance reveals the social role of families*

PubMed Central

Martin, Molly A.

2009-01-01

According to behavioral genetics research, the intergenerational correlation in weight derives solely from shared genetic predispositions, but complete genetic determinism contradicts the scientific consensus that social and behavioral change underlies the modern obesity epidemic. To address this conundrum, this article utilizes sibling data from the National Longitudinal Study of Adolescent Health and extends structural equation sibling models to incorporate siblings’ genetic relationships to explore the role of families’ social characteristics for adolescent weight. The article is the first to demonstrate that the association between parents’ obesity and adolescent weight is both social and genetic. Furthermore, by incorporating genetic information, the shared and social origins of the correlation between inactivity and weight are better revealed. PMID:19569401

Cannabis controversies: how genetics can inform the study of comorbidity.

PubMed

Agrawal, Arpana; Lynskey, Michael T

2014-03-01

To review three key and controversial comorbidities of cannabis use-other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective. Selective review. Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. © 2014 Society for the Study of Addiction.

Cannabis Controversies: How genetics can inform the study of comorbidity

PubMed Central

Agrawal, Arpana; Lynskey, Michael T.

2014-01-01

Aims To review three key and controversial comorbidities of cannabis use – other illicit drug use, psychosis and depression as well as suicide, from a genetically informed perspective. Design Selective review. Results Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Conclusions Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. PMID:24438181

Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation.

PubMed

Xia, Charley; Amador, Carmen; Huffman, Jennifer; Trochet, Holly; Campbell, Archie; Porteous, David; Hastie, Nicholas D; Hayward, Caroline; Vitart, Veronique; Navarro, Pau; Haley, Chris S

2016-02-01

Genome-wide association studies have successfully identified thousands of loci for a range of human complex traits and diseases. The proportion of phenotypic variance explained by significant associations is, however, limited. Given the same dense SNP panels, mixed model analyses capture a greater proportion of phenotypic variance than single SNP analyses but the total is generally still less than the genetic variance estimated from pedigree studies. Combining information from pedigree relationships and SNPs, we examined 16 complex anthropometric and cardiometabolic traits in a Scottish family-based cohort comprising up to 20,000 individuals genotyped for ~520,000 common autosomal SNPs. The inclusion of related individuals provides the opportunity to also estimate the genetic variance associated with pedigree as well as the effects of common family environment. Trait variation was partitioned into SNP-associated and pedigree-associated genetic variation, shared nuclear family environment, shared couple (partner) environment and shared full-sibling environment. Results demonstrate that trait heritabilities vary widely but, on average across traits, SNP-associated and pedigree-associated genetic effects each explain around half the genetic variance. For most traits the recently-shared environment of couples is also significant, accounting for ~11% of the phenotypic variance on average. On the other hand, the environment shared largely in the past by members of a nuclear family or by full-siblings, has a more limited impact. Our findings point to appropriate models to use in future studies as pedigree-associated genetic effects and couple environmental effects have seldom been taken into account in genotype-based analyses. Appropriate description of the trait variation could help understand causes of intra-individual variation and in the detection of contributing loci and environmental factors.

THE LIABILITY FORMS OF THE MEDICAL PERSONNEL.

PubMed

Bărcan, Cristian

2015-01-01

Current legislation, namely Law no. 95/2006 on healthcare reform in the medical malpractice domain stipulates that medical staff can be held accountable in the following forms: disciplinary liability, administrative liability, civil liability and criminal liability. Each form of legal liability presents its features, aspects that are found mainly in the procedural rules. However, the differences between the various legal forms of liability are not met only in the procedural rules but also in their effects and consequences. It is necessary to know what the procedure for disciplinary responsibility, administrative liability, civil liability, or criminal liability is. In addition to the differentiation determined by the consequences that may arise from the different forms of legal liability, it is important to know the competent authorities to investigate a case further and the solutions which various public institutions can take regarding the medical staff. Depending on the type of legal liability, authorities have a specialized authority. If the Disciplinary Committee is encountered at the College of Physicians, it may not intervene in cases before the monitoring and competence for malpractice cases Committee. The latter two committees cannot intervene directly in the legal assessment of civil or criminal cases, as no criminal investigation authorities cannot intervene in strictly civilian cases. Therefore, the importance of knowing the competent institutions is imperative.

46 CFR 298.38 - Partnership agreements and limited liability company agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Partnership agreements and limited liability company... liability company agreements. Partnership and limited liability company agreements must be in form and...) Duration of the entity; (b) Adequate partnership or limited liability company funding requirements and...

Sharing the benefits of genetic resources: from biodiversity to human genetics.

PubMed

Schroeder, Doris; Lasén-Díaz, Carolina

2006-12-01

Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed.

Analysis of shared heritability in common disorders of the brain.

PubMed

Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K; Walters, Raymond K; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A; Ripke, Stephan; Wei, Zhi; Yu, Dongmei; Lee, Phil H; Turley, Patrick; Grenier-Boley, Benjamin; Chouraki, Vincent; Kamatani, Yoichiro; Berr, Claudine; Letenneur, Luc; Hannequin, Didier; Amouyel, Philippe; Boland, Anne; Deleuze, Jean-François; Duron, Emmanuelle; Vardarajan, Badri N; Reitz, Christiane; Goate, Alison M; Huentelman, Matthew J; Kamboh, M Ilyas; Larson, Eric B; Rogaeva, Ekaterina; St George-Hyslop, Peter; Hakonarson, Hakon; Kukull, Walter A; Farrer, Lindsay A; Barnes, Lisa L; Beach, Thomas G; Demirci, F Yesim; Head, Elizabeth; Hulette, Christine M; Jicha, Gregory A; Kauwe, John S K; Kaye, Jeffrey A; Leverenz, James B; Levey, Allan I; Lieberman, Andrew P; Pankratz, Vernon S; Poon, Wayne W; Quinn, Joseph F; Saykin, Andrew J; Schneider, Lon S; Smith, Amanda G; Sonnen, Joshua A; Stern, Robert A; Van Deerlin, Vivianna M; Van Eldik, Linda J; Harold, Denise; Russo, Giancarlo; Rubinsztein, David C; Bayer, Anthony; Tsolaki, Magda; Proitsi, Petra; Fox, Nick C; Hampel, Harald; Owen, Michael J; Mead, Simon; Passmore, Peter; Morgan, Kevin; Nöthen, Markus M; Rossor, Martin; Lupton, Michelle K; Hoffmann, Per; Kornhuber, Johannes; Lawlor, Brian; McQuillin, Andrew; Al-Chalabi, Ammar; Bis, Joshua C; Ruiz, Agustin; Boada, Mercè; Seshadri, Sudha; Beiser, Alexa; Rice, Kenneth; van der Lee, Sven J; De Jager, Philip L; Geschwind, Daniel H; Riemenschneider, Matthias; Riedel-Heller, Steffi; Rotter, Jerome I; Ransmayr, Gerhard; Hyman, Bradley T; Cruchaga, Carlos; Alegret, Montserrat; Winsvold, Bendik; Palta, Priit; Farh, Kai-How; Cuenca-Leon, Ester; Furlotte, Nicholas; Kurth, Tobias; Ligthart, Lannie; Terwindt, Gisela M; Freilinger, Tobias; Ran, Caroline; Gordon, Scott D; Borck, Guntram; Adams, Hieab H H; Lehtimäki, Terho; Wedenoja, Juho; Buring, Julie E; Schürks, Markus; Hrafnsdottir, Maria; Hottenga, Jouke-Jan; Penninx, Brenda; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Hämäläinen, Eija; Huang, Hailiang; Huang, Jie; Sandor, Cynthia; Webber, Caleb; Muller-Myhsok, Bertram; Schreiber, Stefan; Salomaa, Veikko; Loehrer, Elizabeth; Göbel, Hartmut; Macaya, Alfons; Pozo-Rosich, Patricia; Hansen, Thomas; Werge, Thomas; Kaprio, Jaakko; Metspalu, Andres; Kubisch, Christian; Ferrari, Michel D; Belin, Andrea C; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret; Eriksson, Nicholas; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Avbersek, Andreja; Baum, Larry; Berkovic, Samuel; Bradfield, Jonathan; Buono, Russell; Catarino, Claudia B; Cossette, Patrick; De Jonghe, Peter; Depondt, Chantal; Dlugos, Dennis; Ferraro, Thomas N; French, Jacqueline; Hjalgrim, Helle; Jamnadas-Khoda, Jennifer; Kälviäinen, Reetta; Kunz, Wolfram S; Lerche, Holger; Leu, Costin; Lindhout, Dick; Lo, Warren; Lowenstein, Daniel; McCormack, Mark; Møller, Rikke S; Molloy, Anne; Ng, Ping-Wing; Oliver, Karen; Privitera, Michael; Radtke, Rodney; Ruppert, Ann-Kathrin; Sander, Thomas; Schachter, Steven; Schankin, Christoph; Scheffer, Ingrid; Schoch, Susanne; Sisodiya, Sanjay M; Smith, Philip; Sperling, Michael; Striano, Pasquale; Surges, Rainer; Thomas, G Neil; Visscher, Frank; Whelan, Christopher D; Zara, Federico; Heinzen, Erin L; Marson, Anthony; Becker, Felicitas; Stroink, Hans; Zimprich, Fritz; Gasser, Thomas; Gibbs, Raphael; Heutink, Peter; Martinez, Maria; Morris, Huw R; Sharma, Manu; Ryten, Mina; Mok, Kin Y; Pulit, Sara; Bevan, Steve; Holliday, Elizabeth; Attia, John; Battey, Thomas; Boncoraglio, Giorgio; Thijs, Vincent; Chen, Wei-Min; Mitchell, Braxton; Rothwell, Peter; Sharma, Pankaj; Sudlow, Cathie; Vicente, Astrid; Markus, Hugh; Kourkoulis, Christina; Pera, Joana; Raffeld, Miriam; Silliman, Scott; Boraska Perica, Vesna; Thornton, Laura M; Huckins, Laura M; William Rayner, N; Lewis, Cathryn M; Gratacos, Monica; Rybakowski, Filip; Keski-Rahkonen, Anna; Raevuori, Anu; Hudson, James I; Reichborn-Kjennerud, Ted; Monteleone, Palmiero; Karwautz, Andreas; Mannik, Katrin; Baker, Jessica H; O'Toole, Julie K; Trace, Sara E; Davis, Oliver S P; Helder, Sietske G; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Danner, Unna N; van Elburg, Annemarie A; Clementi, Maurizio; Forzan, Monica; Docampo, Elisa; Lissowska, Jolanta; Hauser, Joanna; Tortorella, Alfonso; Maj, Mario; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Papezova, Hana; Yilmaz, Zeynep; Wagner, Gudrun; Cohen-Woods, Sarah; Herms, Stefan; Julià, Antonio; Rabionet, Raquel; Dick, Danielle M; Ripatti, Samuli; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri J; Steen, Vidar M; Pinto, Dalila; Scherer, Stephen W; Aschauer, Harald; Schosser, Alexandra; Alfredsson, Lars; Padyukov, Leonid; Halmi, Katherine A; Mitchell, James; Strober, Michael; Bergen, Andrew W; Kaye, Walter; Szatkiewicz, Jin Peng; Cormand, Bru; Ramos-Quiroga, Josep Antoni; Sánchez-Mora, Cristina; Ribasés, Marta; Casas, Miguel; Hervas, Amaia; Arranz, Maria Jesús; Haavik, Jan; Zayats, Tetyana; Johansson, Stefan; Williams, Nigel; Dempfle, Astrid; Rothenberger, Aribert; Kuntsi, Jonna; Oades, Robert D; Banaschewski, Tobias; Franke, Barbara; Buitelaar, Jan K; Arias Vasquez, Alejandro; Doyle, Alysa E; Reif, Andreas; Lesch, Klaus-Peter; Freitag, Christine; Rivero, Olga; Palmason, Haukur; Romanos, Marcel; Langley, Kate; Rietschel, Marcella; Witt, Stephanie H; Dalsgaard, Soeren; Børglum, Anders D; Waldman, Irwin; Wilmot, Beth; Molly, Nikolas; Bau, Claiton H D; Crosbie, Jennifer; Schachar, Russell; Loo, Sandra K; McGough, James J; Grevet, Eugenio H; Medland, Sarah E; Robinson, Elise; Weiss, Lauren A; Bacchelli, Elena; Bailey, Anthony; Bal, Vanessa; Battaglia, Agatino; Betancur, Catalina; Bolton, Patrick; Cantor, Rita; Celestino-Soper, Patrícia; Dawson, Geraldine; De Rubeis, Silvia; Duque, Frederico; Green, Andrew; Klauck, Sabine M; Leboyer, Marion; Levitt, Pat; Maestrini, Elena; Mane, Shrikant; De-Luca, Daniel Moreno-; Parr, Jeremy; Regan, Regina; Reichenberg, Abraham; Sandin, Sven; Vorstman, Jacob; Wassink, Thomas; Wijsman, Ellen; Cook, Edwin; Santangelo, Susan; Delorme, Richard; Rogé, Bernadette; Magalhaes, Tiago; Arking, Dan; Schulze, Thomas G; Thompson, Robert C; Strohmaier, Jana; Matthews, Keith; Melle, Ingrid; Morris, Derek; Blackwood, Douglas; McIntosh, Andrew; Bergen, Sarah E; Schalling, Martin; Jamain, Stéphane; Maaser, Anna; Fischer, Sascha B; Reinbold, Céline S; Fullerton, Janice M; Guzman-Parra, José; Mayoral, Fermin; Schofield, Peter R; Cichon, Sven; Mühleisen, Thomas W; Degenhardt, Franziska; Schumacher, Johannes; Bauer, Michael; Mitchell, Philip B; Gershon, Elliot S; Rice, John; Potash, James B; Zandi, Peter P; Craddock, Nick; Ferrier, I Nicol; Alda, Martin; Rouleau, Guy A; Turecki, Gustavo; Ophoff, Roel; Pato, Carlos; Anjorin, Adebayo; Stahl, Eli; Leber, Markus; Czerski, Piotr M; Cruceanu, Cristiana; Jones, Ian R; Posthuma, Danielle; Andlauer, Till F M; Forstner, Andreas J; Streit, Fabian; Baune, Bernhard T; Air, Tracy; Sinnamon, Grant; Wray, Naomi R; MacIntyre, Donald J; Porteous, David; Homuth, Georg; Rivera, Margarita; Grove, Jakob; Middeldorp, Christel M; Hickie, Ian; Pergadia, Michele; Mehta, Divya; Smit, Johannes H; Jansen, Rick; de Geus, Eco; Dunn, Erin; Li, Qingqin S; Nauck, Matthias; Schoevers, Robert A; Beekman, Aartjan Tf; Knowles, James A; Viktorin, Alexander; Arnold, Paul; Barr, Cathy L; Bedoya-Berrio, Gabriel; Bienvenu, O Joseph; Brentani, Helena; Burton, Christie; Camarena, Beatriz; Cappi, Carolina; Cath, Danielle; Cavallini, Maria; Cusi, Daniele; Darrow, Sabrina; Denys, Damiaan; Derks, Eske M; Dietrich, Andrea; Fernandez, Thomas; Figee, Martijn; Freimer, Nelson; Gerber, Gloria; Grados, Marco; Greenberg, Erica; Hanna, Gregory L; Hartmann, Andreas; Hirschtritt, Matthew E; Hoekstra, Pieter J; Huang, Alden; Huyser, Chaim; Illmann, Cornelia; Jenike, Michael; Kuperman, Samuel; Leventhal, Bennett; Lochner, Christine; Lyon, Gholson J; Macciardi, Fabio; Madruga-Garrido, Marcos; Malaty, Irene A; Maras, Athanasios; McGrath, Lauren; Miguel, Eurípedes C; Mir, Pablo; Nestadt, Gerald; Nicolini, Humberto; Okun, Michael S; Pakstis, Andrew; Paschou, Peristera; Piacentini, John; Pittenger, Christopher; Plessen, Kerstin; Ramensky, Vasily; Ramos, Eliana M; Reus, Victor; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Roessner, Veit; Rosário, Maria; Samuels, Jack F; Sandor, Paul; Stein, Dan J; Tsetsos, Fotis; Van Nieuwerburgh, Filip; Weatherall, Sarah; Wendland, Jens R; Wolanczyk, Tomasz; Worbe, Yulia; Zai, Gwyneth; Goes, Fernando S; McLaughlin, Nicole; Nestadt, Paul S; Grabe, Hans-Jorgen; Depienne, Christel; Konkashbaev, Anuar; Lanzagorta, Nuria; Valencia-Duarte, Ana; Bramon, Elvira; Buccola, Nancy; Cahn, Wiepke; Cairns, Murray; Chong, Siow A; Cohen, David; Crespo-Facorro, Benedicto; Crowley, James; Davidson, Michael; DeLisi, Lynn; Dinan, Timothy; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Haan, Lieuwe; Hougaard, David; Karachanak-Yankova, Sena; Khrunin, Andrey; Klovins, Janis; Kučinskas, Vaidutis; Lee Chee Keong, Jimmy; Limborska, Svetlana; Loughland, Carmel; Lönnqvist, Jouko; Maher, Brion; Mattheisen, Manuel; McDonald, Colm; Murphy, Kieran C; Nenadic, Igor; van Os, Jim; Pantelis, Christos; Pato, Michele; Petryshen, Tracey; Quested, Digby; Roussos, Panos; Sanders, Alan R; Schall, Ulrich; Schwab, Sibylle G; Sim, Kang; So, Hon-Cheong; Stögmann, Elisabeth; Subramaniam, Mythily; Toncheva, Draga; Waddington, John; Walters, James; Weiser, Mark; Cheng, Wei; Cloninger, Robert; Curtis, David; Gejman, Pablo V; Henskens, Frans; Mattingsdal, Morten; Oh, Sang-Yun; Scott, Rodney; Webb, Bradley; Breen, Gerome; Churchhouse, Claire; Bulik, Cynthia M; Daly, Mark; Dichgans, Martin; Faraone, Stephen V; Guerreiro, Rita; Holmans, Peter; Kendler, Kenneth S; Koeleman, Bobby; Mathews, Carol A; Price, Alkes; Scharf, Jeremiah; Sklar, Pamela; Williams, Julie; Wood, Nicholas W; Cotsapas, Chris; Palotie, Aarno; Smoller, Jordan W; Sullivan, Patrick; Rosand, Jonathan; Corvin, Aiden; Neale, Benjamin M

2018-06-22

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts

PubMed Central

Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

2013-01-01

Objective To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. Materials and methods As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Results Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Discussion Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. Conclusion The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care. PMID:22865671

Adults' perceptions of genetic counseling and genetic testing.

PubMed

Houfek, Julia Fisco; Soltis-Vaughan, Brigette S; Atwood, Jan R; Reiser, Gwendolyn M; Schaefer, G Bradley

2015-02-01

This study described the perceptions of genetic counseling and testing of adults (N = 116) attending a genetic education program. Understanding perceptions of genetic counseling, including the importance of counseling topics, will contribute to patient-focused care as clinical genetic applications for common, complex disorders evolve. Participants completed a survey addressing: the importance of genetic counseling topics, benefits and negative effects of genetic testing, and sharing test results. Topics addressing practical information about genetic conditions were rated most important; topics involving conceptual genetic/genomic principles were rated least important. The most frequently identified benefit and negative effect of testing were prevention/early detection/treatment and psychological distress. Participants perceived that they were more likely to share test results with first-degree than other relatives. Findings suggest providing patients with practical information about genetic testing and genetic contributions to disease, while also determining whether their self-care abilities would be enhanced by teaching genetic/genomic principles. Copyright © 2014 Elsevier Inc. All rights reserved.

29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

Environmental liability and redevelopment of old industrial land.

PubMed

Sigman, Hilary

2010-01-01

Many communities are concerned about the reuse of potentially contaminated land (brownfields) and believe that environmental liability is a hindrance to redevelopment. However, with land price adjustments, liability might not impede the reuse of this land. This article studies state liability rules-specifically, strict liability and joint and several liability-that affect the level and distribution of expected costs of private cleanup. It explores the effects of this variation on industrial land prices and vacancy rates and on reported brownfields in a panel of cities across the United States. In the estimated equations, joint and several liability reduces land prices and increases vacancy rates in central cities. The results suggest that liability is at least partly capitalized but does still deter redevelopment.

Genes, Culture and Conservatism-A Psychometric-Genetic Approach.

PubMed

Schwabe, Inga; Jonker, Wilfried; van den Berg, Stéphanie M

2016-07-01

The Wilson-Patterson conservatism scale was psychometrically evaluated using homogeneity analysis and item response theory models. Results showed that this scale actually measures two different aspects in people: on the one hand people vary in their agreement with either conservative or liberal catch-phrases and on the other hand people vary in their use of the "?" response category of the scale. A 9-item subscale was constructed, consisting of items that seemed to measure liberalism, and this subscale was subsequently used in a biometric analysis including genotype-environment interaction, correcting for non-homogeneous measurement error. Biometric results showed significant genetic and shared environmental influences, and significant genotype-environment interaction effects, suggesting that individuals with a genetic predisposition for conservatism show more non-shared variance but less shared variance than individuals with a genetic predisposition for liberalism.

Shared Genetic Contributions to Anxiety Disorders and Pathological Gambling in a Male Population

PubMed Central

Giddens, Justine L.; Xian, Hong; Scherrer, Jeffrey F.; Eisen, Seth A.; Potenza, Marc N.

2013-01-01

Background Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Method Data from the Vietnam Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). Results While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (ra =0.53). In contrast, substantial correlations were observed between both the genetic (ra=0.34) and unique environmental (re =0.31) contributions to PG and PD. Limitations Results may be limited to middle aged males. Conclusions The existence of shared genetic contributions between PG and both GAD and PD suggest that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women, adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. PMID:21481943

Shared genetic contributions to anxiety disorders and pathological gambling in a male population.

PubMed

Giddens, Justine L; Xian, Hong; Scherrer, Jeffrey F; Eisen, Seth A; Potenza, Marc N

2011-08-01

Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD. Results may be limited to middle aged males. The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. Copyright © 2011. Published by Elsevier B.V.

Genetic and environmental influences on affiliation with deviant peers during adolescence and early adulthood.

PubMed

Tarantino, Nicholas; Tully, Erin C; Garcia, Sarah E; South, Susan; Iacono, William G; McGue, Matt

2014-03-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youths exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence has suggested that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at 3 discrete ages: 15, 18, and 21 years of age. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping, whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Genetic and Environmental Influences on Affiliation with Deviant Peers during Adolescence and Early Adulthood

PubMed Central

Tarantino, Nicholas; Tully, Erin C.; Garcia, Sarah E.; South, Susan; Iacono, William G.; McGue, Matt

2014-01-01

Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youth exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence suggests that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at three discrete ages-15-, 18-, and 21-years-old. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PMID:24015689

Superfund awakes in state supreme courts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutherland, D.

1998-01-01

Superfund, often referred to as a sleeping giant, is waking up in state courts with rulings the insurance industry is on the hook for a large share of the nation`s environmental cleanup. While Congress has been quagmired in legislative reauthorization attempts, 40% of the state supreme courts (20 states) have passed laws favoring policyholders of comprehensive general liability insurance (CGL) to be compensated for their cleanup and litigation costs. These rulings vary in terms from state to state, but their collective action is giving the insurance industry grave concerns because of the increase in settlements with CGL policyholders.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allan; Mills, Evan; Vine, Edward.

The promotion of technologies and services for insurance loss reduction and loss prevention is as old as the fields of insurance and risk management. This report addresses a new category of risk management opportunity involving technologies and procedures that use energy more efficiently or supply renewable energy. While the economic benefits of these measures are of interest to energy consumers seeking to reduce their energy expenditures, we have found that they also offer a novel and largely untapped pathway for achieving traditional risk management objectives. Most of the technologies described in this report were supported by government- sponsored RD Dmore » programs over many years of effort. These technologies have many benefits, including insurance loss reduction and prevention. The insurance and risk management communities could take advantage of these technologies, either independently or in cost-sharing partnerships with existing R D programs. In this report, we present a compilation of energy-efficiency and renewable energy projects (e.g., energy-efficient halogen torchiere replacements) and techniques (e.g., infrared cameras to detect fire hazards) that are currently being investigated at the U.S. Department of Energy's national laboratories and which the insurance and risk management communities could encourage their customers to use to address their short-term and long-term needs. Once the loss-prevention benefits of these technologies and techniques (many of which are not yet available in the marketplace) are sufficiently demonstrated, insurers can promote their use through informational programs and perhaps financial incentives (e.g., risk-adjusted insurance premium schemes) through the insurance regulatory and rate-making processes. We identified 78 technologies and techniques being investigated by nine national laboratories which can help to reduce insurance losses and manage risks, especially those associated with power failures, fire and wind damage, and home or workplace indoor air quality hazards. All help to reduce insurance losses in one or more of the following categories: boiler and machinery, builder's risk, business interruption, commercial property insurance, completed operations liability, comprehensive general liability, contractors liability, environmental liability, product liability, professional liability, service interruption, workers' compensation, health/life insurance, and homeowners insurance. We identify examples of existing collaborations between the national laboratories and the insurance industry, and indicate research activities being conducted by the insurance and risk management communities that would benefit from the work of the national laboratories. We also describe some of the risk factors associated with energy-efficient and renewable energy technologies. For the future, significant progress could be made through interdisciplinary collaborative applied research (i.e., integrating the actuarial sciences with the physical or engineering sciences). This collaboration could be sponsored jointly by the U.S. Department of Energy and the insurance and risk management communities (as well as working through the insurance regulatory and rate-making processes).« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allan; Mills, Evan; Vine, Edward

The promotion of technologies and services for insurance loss reduction and loss prevention is as old as the fields of insurance and risk management. This report addresses a new category of risk management opportunity involving technologies and procedures that use energy more efficiently or supply renewable energy. While the economic benefits of these measures are of interest to energy consumers seeking to reduce their energy expenditures, we have found that they also offer a novel and largely untapped pathway for achieving traditional risk management objectives. Most of the technologies described in this report were supported by government- sponsored RD&D programsmore » over many years of effort. These technologies have many benefits, including insurance loss reduction and prevention. The insurance and risk management communities could take advantage of these technologies, either independently or in cost-sharing partnerships with existing R&D programs. In this report, we present a compilation of energy-efficiency and renewable energy projects (e.g., energy-efficient halogen torchiere replacements) and techniques (e.g., infrared cameras to detect fire hazards) that are currently being investigated at the U.S. Department of Energy's national laboratories and which the insurance and risk management communities could encourage their customers to use to address their short-term and long-term needs. Once the loss-prevention benefits of these technologies and techniques (many of which are not yet available in the marketplace) are sufficiently demonstrated, insurers can promote their use through informational programs and perhaps financial incentives (e.g., risk-adjusted insurance premium schemes) through the insurance regulatory and rate-making processes. We identified 78 technologies and techniques being investigated by nine national laboratories which can help to reduce insurance losses and manage risks, especially those associated with power failures, fire and wind damage, and home or workplace indoor air quality hazards. All help to reduce insurance losses in one or more of the following categories: boiler and machinery, builder's risk, business interruption, commercial property insurance, completed operations liability, comprehensive general liability, contractors liability, environmental liability, product liability, professional liability, service interruption, workers' compensation, health/life insurance, and homeowners insurance. We identify examples of existing collaborations between the national laboratories and the insurance industry, and indicate research activities being conducted by the insurance and risk management communities that would benefit from the work of the national laboratories. We also describe some of the risk factors associated with energy-efficient and renewable energy technologies. For the future, significant progress could be made through interdisciplinary collaborative applied research (i.e., integrating the actuarial sciences with the "physical" or "engineering" sciences). This collaboration could be sponsored jointly by the U.S. Department of Energy and the insurance and risk management communities (as well as working through the insurance regulatory and rate-making processes).« less

Genetic and Environmental Contributions to Behavioral Stability and Change in Children 6-36 months of Age Using Louisville Twin Study Data.

PubMed

Davis, Deborah Winders; Finkel, Deborah; Turkheimer, Eric; Dickens, William

2015-11-01

The Infant Behavior Record (IBR) from the Bayley Scales of Infant Development has been used to study behavioral development since the 1960s. Matheny (1983) examined behavioral development at 6, 12, 18, and 24 months from the Louisville Twin Study (LTS). The extracted temperament scales included Task Orientation, Affect-Extraversion, and Activity. He concluded that monozygotic twins were more similar than same-sex dizygotic twins on these dimensions. Since this seminal work was published, a larger LTS sample and more advanced analytical methods are available. In the current analyses, Choleksy decomposition was applied to behavioral data (n = 1231) from twins 6-36 months. Different patterns of genetic continuity vs genetic innovations were identified for each IBR scale. Single common genetic and shared environmental factors explained cross-age twin similarity in the Activity scale. Multiple shared environmental factors and a single genetic factor coming on line at age 18 months contributed to Affect-Extraversion. A single shared environmental factor and multiple genetic factors explained cross-age twin similarity in Task Orientation.

Education Modifies Genetic and Environmental Influences on BMI

PubMed Central

Johnson, Wendy; Kyvik, Kirsten Ohm; Skytthe, Axel; Deary, Ian J.; Sørensen, Thorkild I. A.

2011-01-01

Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height2) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were −.13 in women, −.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity. PMID:21283825

Harmonizing the interpretation of genetic variants across the world: the Malaysian experience.

PubMed

Hassan, Nik Norliza Nik; Plazzer, John-Paul; Smith, Timothy D; Halim-Fikri, Hashim; Macrae, Finlay; Zubaidi, A A L; Zilfalil, Bin Alwi

2016-02-26

Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants. Somatic variants, mitochondrial variants and other types of genetic variation have corresponding databases which are not covered here, as they have specific issues that do not necessarily apply to germline variations. The ethical, legal, social issues, intellectual property, ownership of the data, information technology implementation, and efforts to improve the standards and systems used in data sharing are discussed. An overarching framework such as provided by the Human Variome Project to co-ordinate activities is invaluable. Country Nodes, such as MyHVP, enable human gene variation associated with human diseases to be collected, stored and shared by all disciplines (clinicians, molecular biologists, pathologists, bioinformaticians) for a consistent interpretation of genetic variants locally and across the world.

The gene-environmental architecture of the development of adolescent substance use.

PubMed

Vitaro, Frank; Dickson, Daniel J; Brendgen, Mara; Laursen, Brett; Dionne, Ginette; Boivin, Michel

2018-02-19

Using a longitudinal twin design and a latent growth curve/autoregressive approach, this study examined the genetic-environmental architecture of substance use across adolescence. Self-reports of substance use (i.e. alcohol, marijuana) were collected at ages 13, 14, 15, and 17 years from 476 twin pairs (475 boys, 477 girls) living in the Province of Quebec, Canada. Substance use increased linearly across the adolescent years. ACE modeling revealed that genetic, as well as shared and non-shared environmental factors explained the overall level of substance use and that these same factors also partly accounted for growth in substance use from age 13 to 17. Additional genetic factors predicted the growth in substance use. Finally, autoregressive effects revealed age-specific non-shared environmental influences and, to a lesser degree, age-specific genetic influences, which together accounted for the stability of substance use across adolescence. The results support and expand the notion that genetic and environmental influences on substance use during adolescence are both developmentally stable and developmentally dynamic.

Genetic and Environmental Influences on Depressive Symptoms in Chinese Adolescents

PubMed Central

Chen, Jie; Li, Xinying; Natsuaki, Misaki N.; Leve, Leslie D.; Harold, Gordon T.

2016-01-01

Adolescent depression is common and has become a major public health concern in China, yet little research has examined the etiology of depression in Chinese adolescents. In the present study, genetic and environmental influences on Chinese adolescent depressive symptoms were investigated in 1181 twin pairs residing in Beijing, China (ages 11 to 19 years). Child- and parent-versions of the Children’s Depression Inventory (CDI) were used to measure adolescents’ depressive symptoms. For self-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 50%, 5%, and 45% of the variation in depressive symptoms, respectively; for parent-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 51%, 18%, and 31% of the variation, respectively. These estimates are generally consistent with previous findings in Western adolescents, supporting the cross-cultural generalizability of etiological model of adolescent depression. Neither qualitative nor quantitative sex differences were found in the etiological model. Future studies are needed to investigate how genes and environments work together (gene-environment interaction, gene-environment correlation) to influence depression in Chinese adolescents. PMID:24311200

Genetic and environmental influences on depressive symptoms in Chinese adolescents.

PubMed

Chen, Jie; Li, Xinying; Natsuaki, Misaki N; Leve, Leslie D; Harold, Gordon T

2014-01-01

Adolescent depression is common and has become a major public health concern in China, yet little research has examined the etiology of depression in Chinese adolescents. In the present study, genetic and environmental influences on Chinese adolescent depressive symptoms were investigated in 1,181 twin pairs residing in Beijing, China (ages 11-19 years). Child- and parent-versions of the children's depression inventory were used to measure adolescents' depressive symptoms. For self-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 50, 5, and 45 % of the variation in depressive symptoms, respectively; for parent-reports, genetic factors, shared environmental factors, and non-shared environmental factors accounted for 51, 18, and 31 % of the variation, respectively. These estimates are generally consistent with previous findings in Western adolescents, supporting the cross-cultural generalizability of etiological model of adolescent depression. Neither qualitative nor quantitative sex differences were found in the etiological model. Future studies are needed to investigate how genes and environments work together (gene-environment interaction, gene-environment correlation) to influence depression in Chinese adolescents.

Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities.

PubMed

Waitkus, Matthew S; Pirozzi, Christopher J; Moure, Casey J; Diplas, Bill H; Hansen, Landon J; Carpenter, Austin B; Yang, Rui; Wang, Zhaohui; Ingram, Brian O; Karoly, Edward D; Mohney, Robert P; Spasojevic, Ivan; McLendon, Roger E; Friedman, Henry S; He, Yiping; Bigner, Darell D; Yan, Hai

2018-01-01

Hotspot mutations in the isocitrate dehydrogenase 1 ( IDH1 ) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malignant gliomas, IDH1 R132H expression induces widespread metabolic reprogramming, possibly requiring compensatory mechanisms to sustain the normal biosynthetic requirements of actively proliferating tumor cells. We used genetically engineered mouse models of glioma and quantitative metabolomics to investigate IDH1 R132H -dependent metabolic reprogramming and its potential to induce biosynthetic liabilities that can be exploited for glioma therapy. In gliomagenic neural progenitor cells, IDH1 R132H expression increased the abundance of dipeptide metabolites, depleted key tricarboxylic acid cycle metabolites, and slowed progression of murine gliomas. Notably, expression of glutamate dehydrogenase GDH2, a hominoid-specific enzyme with relatively restricted expression to the brain, was critically involved in compensating for IDH1 R132H -induced metabolic alterations and promoting IDH1 R132H glioma growth. Indeed, we found that recently evolved amino acid substitutions in the GDH2 allosteric domain conferred its nonredundant, glioma-promoting properties in the presence of IDH1 mutation. Our results indicate that among the unique roles for GDH2 in the human forebrain is its ability to limit IDH1 R132H -mediated metabolic liabilities, thus promoting glioma growth in this context. Results from this study raise the possibility that GDH2-specific inhibition may be a viable therapeutic strategy for gliomas with IDH mutations. Significance: These findings show that the homonid-specific brain enzyme GDH2 may be essential to mitigate metabolic liabilities created by IDH1 mutations in glioma, with possible implications to leverage its therapeutic management by IDH1 inhibitors. Cancer Res; 78(1); 36-50. ©2017 AACR . ©2017 American Association for Cancer Research.

Admixture into and within sub-Saharan Africa.

PubMed

Busby, George Bj; Band, Gavin; Si Le, Quang; Jallow, Muminatou; Bougama, Edith; Mangano, Valentina D; Amenga-Etego, Lucas N; Enimil, Anthony; Apinjoh, Tobias; Ndila, Carolyne M; Manjurano, Alphaxard; Nyirongo, Vysaul; Doumba, Ogobara; Rockett, Kirk A; Kwiatkowski, Dominic P; Spencer, Chris Ca

2016-06-21

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

Differential heritability of adult and juvenile antisocial traits.

PubMed

Lyons, M J; True, W R; Eisen, S A; Goldberg, J; Meyer, J M; Faraone, S V; Eaves, L J; Tsuang, M T

1995-11-01

Studies of adult antisocial behavior or criminality usually find genetic factors to be more important than the family environment, whereas studies of delinquency find the family environment to be more important. We compared DSM-III-R antisocial personality disorder symptoms before vs after the age of 15 years within a sample of twins, rather than comparing across studies. We administered the Diagnostic Interview Schedule Version III-revised by telephone to 3226 pairs of male twins from the Vietnam Era Twin Registry. Biometrical modeling was applied to each symptom of antisocial personality disorder and summary measures of juvenile and adult symptoms. Five juvenile symptoms were significantly heritable, and five were significantly influenced by the shared environment. Eight adult symptoms were significantly heritable, and one was significantly influenced by the shared environment. The shared environment explained about six times more variance in juvenile anti-social traits than in adult traits. Shared environmental influences on adult antisocial traits overlapped entirely with those on juvenile traits. Additive genetic factors explained about six times more variance in adult vs juvenile traits. The juvenile genetic determinants overlapped completely with genetic influences on adult traits. The unique environment (plus measurement error) explained the largest proportion of variance in both juvenile and adult antisocial traits. Characteristics of the shared or family environment that promote antisocial behavior during childhood and early adolescence also promote later antisocial behavior, but to a much lesser extent. Genetic causal factors are much more prominent for adult than for juvenile antisocial traits.

Shared versus distinct genetic contributions of mental wellbeing with depression and anxiety symptoms in healthy twins.

PubMed

Routledge, Kylie M; Burton, Karen L O; Williams, Leanne M; Harris, Anthony; Schofield, Peter R; Clark, C Richard; Gatt, Justine M

2016-10-30

Mental wellbeing and mental illness symptoms are typically conceptualized as opposite ends of a continuum, despite only sharing about a quarter in common variance. We investigated the normative variation in measures of wellbeing and of depression and anxiety in 1486 twins who did not meet clinical criteria for an overt diagnosis. We quantified the shared versus distinct genetic and environmental variance between wellbeing and depression and anxiety symptoms. The majority of participants (93%) reported levels of depression and anxiety symptoms within the healthy range, yet only 23% reported a wellbeing score within the "flourishing" range: the remainder were within the ranges of "moderate" (67%) or "languishing" (10%). In twin models, measures of wellbeing and of depression and anxiety shared 50.09% of variance due to genetic factors and 18.27% due to environmental factors; the rest of the variance was due to unique variation impacting wellbeing or depression and anxiety symptoms. These findings suggest that an absence of clinically-significant symptoms of depression and anxiety does not necessarily indicate that an individual is flourishing. Both unique and shared genetic and environmental factors may determine why some individuals flourish in the absence of symptoms while others do not. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genetic Overlap Between Schizophrenia and Volumes of Hippocampus, Putamen, and Intracranial Volume Indicates Shared Molecular Genetic Mechanisms.

PubMed

Smeland, Olav B; Wang, Yunpeng; Frei, Oleksandr; Li, Wen; Hibar, Derrek P; Franke, Barbara; Bettella, Francesco; Witoelar, Aree; Djurovic, Srdjan; Chen, Chi-Hua; Thompson, Paul M; Dale, Anders M; Andreassen, Ole A

2018-06-06

Schizophrenia (SCZ) is associated with differences in subcortical brain volumes and intracranial volume (ICV). However, little is known about the underlying etiology of these brain alterations. Here, we explored whether brain structure volumes and SCZ share genetic risk factors. Using conditional false discovery rate (FDR) analysis, we integrated genome-wide association study (GWAS) data on SCZ (n = 82315) and GWAS data on 7 subcortical brain volumes and ICV (n = 11840). By conditioning the FDR on overlapping associations, this statistical approach increases power to discover genetic loci. To assess the credibility of our approach, we studied the identified loci in larger GWAS samples on ICV (n = 26577) and hippocampal volume (n = 26814). We observed polygenic overlap between SCZ and volumes of hippocampus, putamen, and ICV. Based on conjunctional FDR < 0.05, we identified 2 loci shared between SCZ and ICV implicating genes FOXO3 (rs10457180) and ITIH4 (rs4687658), 2 loci shared between SCZ and hippocampal volume implicating SLC4A10 (rs4664442) and SPATS2L (rs1653290), and 2 loci shared between SCZ and volume of putamen implicating DCC (rs4632195) and DLG2 (rs11233632). The loci shared between SCZ and hippocampal volume or ICV had not reached significance in the primary GWAS on brain phenotypes. Proving our point of increased power, 2 loci did reach genome-wide significance with ICV (rs10457180) and hippocampal volume (rs4664442) in the larger GWAS. Three of the 6 identified loci are novel for SCZ. Altogether, the findings provide new insights into the relationship between SCZ and brain structure volumes, suggesting that their genetic architectures are not independent.

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots

PubMed Central

Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7–8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry. PMID:28622394

Y-chromosomal analysis of Greek Cypriots reveals a primarily common pre-Ottoman paternal ancestry with Turkish Cypriots.

PubMed

Heraclides, Alexandros; Bashiardes, Evy; Fernández-Domínguez, Eva; Bertoncini, Stefania; Chimonas, Marios; Christofi, Vasilis; King, Jonathan; Budowle, Bruce; Manoli, Panayiotis; Cariolou, Marios A

2017-01-01

Genetics can provide invaluable information on the ancestry of the current inhabitants of Cyprus. A Y-chromosome analysis was performed to (i) determine paternal ancestry among the Greek Cypriot (GCy) community in the context of the Central and Eastern Mediterranean and the Near East; and (ii) identify genetic similarities and differences between Greek Cypriots (GCy) and Turkish Cypriots (TCy). Our haplotype-based analysis has revealed that GCy and TCy patrilineages derive primarily from a single gene pool and show very close genetic affinity (low genetic differentiation) to Calabrian Italian and Lebanese patrilineages. In terms of more recent (past millennium) ancestry, as indicated by Y-haplotype sharing, GCy and TCy share much more haplotypes between them than with any surrounding population (7-8% of total haplotypes shared), while TCy also share around 3% of haplotypes with mainland Turks, and to a lesser extent with North Africans. In terms of Y-haplogroup frequencies, again GCy and TCy show very similar distributions, with the predominant haplogroups in both being J2a-M410, E-M78, and G2-P287. Overall, GCy also have a similar Y-haplogroup distribution to non-Turkic Anatolian and Southwest Caucasian populations, as well as Cretan Greeks. TCy show a slight shift towards Turkish populations, due to the presence of Eastern Eurasian (some of which of possible Ottoman origin) Y-haplogroups. Overall, the Y-chromosome analysis performed, using both Y-STR haplotype and binary Y-haplogroup data puts Cypriot in the middle of a genetic continuum stretching from the Levant to Southeast Europe and reveals that despite some differences in haplotype sharing and haplogroup structure, Greek Cypriots and Turkish Cypriots share primarily a common pre-Ottoman paternal ancestry.

76 FR 13656 - Notice of Submission of Proposed Information Collection to OMB Requirement for Contractors to...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... insurance provide evidence that worker's compensation and general liability, automobile liability insurance... insurance provide evidence that worker's compensation and general liability, automobile liability insurance...

Liability of professional and volunteer mental health practitioners in the wake of disasters: a framework for further considerations.

PubMed

Abdel-Monem, Tarik; Bulling, Denise

2005-01-01

Qualified immunity from civil liability exists for acts of disaster mental health (DMH) practitioners responding to disasters or acts of terrorism. This article reviews current legal regimens dictating civil liability for potentially wrongful acts of DMH professionals and volunteers responding to disasters. Criteria are proposed to inform determinations of civil liability for DMH workers in disaster response, given current legal parameters and established tort law in relevant areas. Specific considerations are examined that potentially implicate direct liability of DMH professionals and volunteers, and vicarious liability of DMH supervisors for actions of volunteer subordinates. The relevance of pre-event DMH planning and operationalization of the plan post-event is linked to considerations of liability. This article concludes with recommendations to minimize liability exposure for DMH workers in response efforts.

Breast Cancer

MedlinePlus

... a genetic counselor, who can review your family health history. A genetic counselor can also discuss the benefits, risks and limitations of genetic testing to assist you with shared decision-making. Risk ...

New developments in the epidemiology and genetics of gout.

PubMed

Zaka, Raihana; Williams, Charlene J

2006-06-01

The prevalence of gout appears to be rapidly increasing worldwide and is no longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk factors include longevity, metabolic syndrome, and new classes of pharmacologic agents. In some ethnic populations, no obvious risk factors can explain the high incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to identify genes associated with gout have included families with defects in purine metabolism, as well as families in whom the occurrence of gout is secondary to renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic kidney disease. Case-control studies of isolated aboriginal cohorts suffering from primary gout have revealed several chromosomal loci that may harbor genes that are important to the development and/or progression of gout.

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

The genetic and environmental etiology of antisocial behavior from childhood to emerging adulthood.

PubMed

Tuvblad, Catherine; Narusyte, Jurgita; Grann, Martin; Sarnecki, Jerzy; Lichtenstein, Paul

2011-09-01

Previous research suggests that both genetic and environmental influences are important for antisocial behavior across the life span, even though the prevalence and incidence of antisocial behavior varies considerably across ages. However, little is known of how genetic and environmental effects influence the development of antisocial behavior. A total of 2,600 male and female twins from the population-based Swedish Twin Registry were included in the present study. Antisocial behavior was measured on four occasions, when twins were 8-9, 13-14, 16-17, and 19-20 years old. Longitudinal analyses of the data were conducted using structural equation modeling. The stability of antisocial behavior over time was explained by a common latent persistent antisocial behavior factor. A common genetic influence accounted for 67% of the total variance in this latent factor, the shared environment explained 26%, and the remaining 7% was due to the non-shared environment. Significant age-specific shared environmental factors were found at ages 13-14 years, suggesting that common experiences (e.g., peers) are important for antisocial behavior at this age. Results from this study show that genetic as well as shared environmental influences are important in antisocial behavior that persists from childhood to emerging adulthood.

Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection.

PubMed

Tarnoki, David Laszlo; Tarnoki, Adam Domonkos; Medda, Emanuela; Littvay, Levente; Lazar, Zsofia; Toccaceli, Virgilia; Fagnani, Corrado; Stazi, Maria Antonietta; Nisticó, Lorenza; Brescianini, Sonia; Penna, Luana; Lucatelli, Pierleone; Boatta, Emanuele; Zini, Chiara; Fanelli, Fabrizio; Baracchini, Claudio; Meneghetti, Giorgio; Koller, Akos; Osztovits, Janos; Jermendy, Gyorgy; Preda, Istvan; Kiss, Robert Gabor; Karlinger, Kinga; Lannert, Agnes; Horvath, Tamas; Schillaci, Giuseppe; Molnar, Andrea Agnes; Garami, Zsolt; Berczi, Viktor; Horvath, Ildiko

2013-06-01

Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FE(NO)) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FE(NO) levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FE(NO) was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aix(ao)) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FE(NO) and Aix(ao) were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FE(NO) with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FE(NO) and Aix(ao) (r = -0.17; 95%CI:-0.32,-0.02). FE(NO) showed a significant negative genetic correlation with Aix(ao) (r(g) = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FE(NO) are explained both by genetic and non-shared environmental effects. Covariance between FE(NO) and Aix(ao) is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.

Shared genetic determinants of axial length and height in children: the Guangzhou twin eye study.

PubMed

Zhang, Jian; Hur, Yoon-Mi; Huang, Wenyong; Ding, Xiaohu; Feng, Ke; He, Mingguang

2011-01-01

To describe the association between axial length (AL) and height and to estimate the extent to which shared genetic or environmental factors influence this covariance. Study participants were recruited from the Guangzhou Twin Registry. Axial length was measured using partial coherence laser interferometry. Height was measured with the participants standing without shoes. We computed twin pairwise correlations and cross-twin cross-trait correlations between AL and height for monozygotic and dizygotic twins and performed model-fitting analyses using a multivariate Cholesky model. The right eye was arbitrarily selected to represent AL of participants. Five hundred sixty-five twin pairs (359 monozygotic and 206 dizygotic) aged 7 to 15 years were available for analysis. Phenotypic correlation between AL and height was 0.46 but decreased to 0.19 after adjusting for age, sex, and age × sex interaction. Bivariate Cholesky model-fitting analyses revealed that 89% of phenotypic correlation was due to shared genetic factors and 11% was due to shared random environmental factors, which includes measurement error. Covariance of AL and height is largely attributable to shared genes. Given that AL is a key determinant of myopia, further work is needed to confirm gene sharing between myopia and stature.

Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity.

PubMed

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates--childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.

Facial affect recognition deficit as a marker of genetic vulnerability to schizophrenia.

PubMed

Alfimova, Margarita V; Abramova, Lilia I; Barhatova, Aleksandra I; Yumatova, Polina E; Lyachenko, Galina L; Golimbet, Vera E

2009-05-01

The aim of this study was to investigate the possibility that affect recognition impairments are associated with genetic liability to schizophrenia. In a group of 55 unaffected relatives of schizophrenia patients (parents and siblings) we examined the capacity to detect facially expressed emotions and its relationship to schizotypal personality, neurocognitive functioning, and the subject's actual emotional state. The relatives were compared with 103 schizophrenia patients and 99 healthy subjects without any family history of psychoses. Emotional stimuli were nine black-and-white photos of actors, who portrayed six basic emotions as well as interest, contempt, and shame. The results evidenced the affect recognition deficit in relatives, though milder than that in patients themselves. No correlation between the deficit and schizotypal personality measured with SPQ was detected in the group of relatives. Neither cognitive functioning, including attention, verbal memory and linguistic ability, nor actual emotional states accounted for their affect recognition impairments. The results suggest that the facial affect recognition deficit in schizophrenia may be related to genetic predisposition to the disorder and may serve as an endophenotype in molecular-genetic studies.

Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development.

PubMed

Stergiakouli, Evie; Davey Smith, George; Martin, Joanna; Skuse, David H; Viechtbauer, Wolfgang; Ring, Susan M; Ronald, Angelica; Evans, David E; Fisher, Simon E; Thapar, Anita; St Pourcain, Beate

2017-01-01

Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) symptoms and autism spectrum disorder (ASD) symptoms have been reported. Cross-trait genetic relationships are, however, subject to dynamic changes during development. We investigated the continuity of genetic overlap between ASD and ADHD symptoms in a general population sample during childhood and adolescence. We also studied uni- and cross-dimensional trait-disorder links with respect to genetic ADHD and ASD risk. Social-communication difficulties ( N  ≤ 5551, Social and Communication Disorders Checklist, SCDC) and combined hyperactive-impulsive/inattentive ADHD symptoms ( N  ≤ 5678, Strengths and Difficulties Questionnaire, SDQ-ADHD) were repeatedly measured in a UK birth cohort (ALSPAC, age 7 to 17 years). Genome-wide summary statistics on clinical ASD (5305 cases; 5305 pseudo-controls) and ADHD (4163 cases; 12,040 controls/pseudo-controls) were available from the Psychiatric Genomics Consortium. Genetic trait variances and genetic overlap between phenotypes were estimated using genome-wide data. In the general population, genetic influences for SCDC and SDQ-ADHD scores were shared throughout development. Genetic correlations across traits reached a similar strength and magnitude (cross-trait r g  ≤ 1, p min   =  3 × 10 -4 ) as those between repeated measures of the same trait (within-trait r g  ≤ 0.94, p min   =  7 × 10 -4 ). Shared genetic influences between traits, especially during later adolescence, may implicate variants in K-RAS signalling upregulated genes ( p -meta = 6.4 × 10 -4 ). Uni-dimensionally, each population-based trait mapped to the expected behavioural continuum: risk-increasing alleles for clinical ADHD were persistently associated with SDQ-ADHD scores throughout development (marginal regression R 2  = 0.084%). An age-specific genetic overlap between clinical ASD and social-communication difficulties during childhood was also shown, as per previous reports. Cross-dimensionally, however, neither SCDC nor SDQ-ADHD scores were linked to genetic risk for disorder. In the general population, genetic aetiologies between social-communication difficulties and ADHD symptoms are shared throughout child and adolescent development and may implicate similar biological pathways that co-vary during development. Within both the ASD and the ADHD dimension, population-based traits are also linked to clinical disorder, although much larger clinical discovery samples are required to reliably detect cross-dimensional trait-disorder relationships.

Borderline personality disorder traits and their relationship with dimensions of normative personality: a web-based cohort and twin study

PubMed Central

Kendler, K. S.; Myers, J.; Reichborn-Kjennerud, T.

2011-01-01

Objective To describe the structure of genetic and environmental risk factors for four dimensions of borderline personality disorder (BPD) and to understand the source of resemblance of these dimensions and normal personality. Method A web-based sample (n = 44,112 including 542 twin pairs) completed items from 4 scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire and the Big Five Inventory. Results A one-factor common pathway model best fits the 4 BPD scales producing a highly heritable latent liability (heritability = 60%) and strong loadings on all 4 dimensions. Affective instability had the lowest trait-specific genetic loading, suggesting that it was a core feature of BPD. A complex pattern of genetic and environmental associations was found between the big five personality traits and BPD dimensions. The strongest genetic correlations with the BPD traits were generally seen for neuroticism (positive), followed by conscientiousness and agreeableness, both negative. Conclusion In the general population, these four BPD dimensions reflect one underlying highly heritable factor. The association between normative personality and dimensions of BPD is complex with high degrees of genetic correlation. PMID:21198457

Borderline personality disorder traits and their relationship with dimensions of normative personality: a web-based cohort and twin study.

PubMed

Kendler, K S; Myers, J; Reichborn-Kjennerud, T

2011-05-01

To describe the structure of genetic and environmental risk factors for four dimensions of borderline personality disorder (BPD) and to understand the source of resemblance of these dimensions and normal personality. A web-based sample (n = 44,112 including 542 twin pairs) completed items from 4 scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire and the Big Five Inventory. A one-factor common pathway model best fits the 4 BPD scales producing a highly heritable latent liability (heritability = 60%) and strong loadings on all 4 dimensions. Affective instability had the lowest trait-specific genetic loading, suggesting that it was a core feature of BPD. A complex pattern of genetic and environmental associations was found between the big five personality traits and BPD dimensions. The strongest genetic correlations with the BPD traits were generally seen for neuroticism (positive), followed by conscientiousness and agreeableness, both negative. In the general population, these four BPD dimensions reflect one underlying highly heritable factor. The association between normative personality and dimensions of BPD is complex with high degrees of genetic correlation. © 2010 John Wiley & Sons A/S.

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

PubMed

Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Genetic considerations in human sex-mate selection: partners share human leukocyte antigen but not short-tandem-repeat identity markers.

PubMed

Israeli, Moshe; Kristt, Don; Nardi, Yuval; Klein, Tirza

2014-05-01

Previous studies support a role for MHC on mating preference, yet it remains unsettled as to whether mating occurs preferentially between individuals sharing human leukocyte antigen (HLA) determinants or not. Investigating sex-mate preferences in the contemporary Israeli population is of further curiosity being a population with distinct genetic characteristics, where multifaceted cultural considerations influence mate selection. Pairs of male-female sex partners were evaluated in three groups. Two groups represented unmarried (n = 1002) or married (n = 308) couples and a control group of fictitious male-female couples. HLA and short-tandem-repeat (STR) genetic identification markers were assessed for the frequency of shared antigens and alleles. Human leukocyte antigen results showed that Class I and/ or Class II single antigen as well as double antigen sharing was more common in sex partners than in control group couples (P < 0.001). Married versus unmarried pairs were not distinguishable. In contrast, STR-DNA markers failed to differentiate between sex-mates and controls (P = 0.78). Sex partnerships shared HLA determinants more frequently than randomly constituted male-female pairs. The observed phenomenon does not reflect a syngenetic background between sex-mates as STR markers were not selectively shared. Thus, sex-mate selection in man may contravene the evolutionary pressure for genetic diversity in regard to HLA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cognitive performance and BMI in childhood: Shared genetic influences between reaction time but not response inhibition

USDA-ARS?s Scientific Manuscript database

The aim of this work is to understand whether shared genetic influences can explain the associationbetween obesity and cognitive performance, including slower and more variable reaction times(RTs) and worse response inhibition. RT on a four-choice RT task and the go/no-go task, and commission errors...

Preschool Drawing and School Mathematics: The Nature of the Association

PubMed Central

Malanchini, M.; Tosto, M.G.; Garfield, V.; Czerwik, A.; Dirik, A.; Arden, R.; Malykh, S.

2016-01-01

The study examined the aetiology of individual differences in early drawing and of its longitudinal association with school mathematics. Participants (N = 14,760), members of the Twins Early Development Study, were assessed on their ability to draw a human figure, including number of features, symmetry and proportionality. Human figure drawing was moderately stable across six months (average r = .40). Individual differences in drawing at age 4½ were influenced by genetic (.21), shared environmental (.30) and non-shared environmental (.49) factors. Drawing was related to later (age 12) mathematical ability (average r = .24). This association was explained by genetic and shared environmental factors that also influenced general intelligence. Some genetic factors, unrelated to intelligence, also contributed to individual differences in drawing. PMID:27079561

The College Professor's Professional Liability

ERIC Educational Resources Information Center

Griggs, Walter S.; Rubin, Harvey W.

1977-01-01

The growing number of professional liability suits against professors warrants a close examination of the need for and provisions of available insurance coverage. The evolution of tort liability, the question of negligence, and the professional liability policy are discussed. (LBH)

Genetic counseling

MedlinePlus

... this page: //medlineplus.gov/ency/patientinstructions/000510.htm Genetic counseling To use the sharing features on this ... cystic fibrosis or Down syndrome. Who May Want Genetic Counseling? It is up to you whether or ...

Genetic Counseling

MedlinePlus

... Testing Evaluating Genomic Tests Epidemiology Pathogen Genomics Resources Genetic Counseling Recommend on Facebook Tweet Share Compartir In ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

Exploring links among imitation, mental development, and temperament

PubMed Central

Fenstermacher, Susan K.; Saudino, Kimberly J.

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children’s imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique. PMID:27840593

Exploring links among imitation, mental development, and temperament.

PubMed

Fenstermacher, Susan K; Saudino, Kimberly J

2016-01-01

Links among imitation, performance on a standardized test of intellectual development, and laboratory-assessed temperament were explored in 311 24-month old twin pairs. Moderate phenotypic associations were found between imitation, mental development, and temperament dimensions of Affect/Extraversion and Task Orientation. Covariance between imitation and mental development reflected genetic and shared environmental influences, whereas associations between imitation and temperament reflected genetic, shared, and nonshared environmental influences. Genetic factors linking imitation and temperament were the same as those linking temperament and mental development. Nonetheless, approximately 62% of total genetic variance on imitation was independent of genetic influences on mental development and temperament, suggesting that young children's imitation is not simply an index of general cognitive ability or dispositional style but has many underlying genetic influences that are unique.

Improved obstetric safety through programmatic collaboration.

PubMed

Goffman, Dena; Brodman, Michael; Friedman, Arnold J; Minkoff, Howard; Merkatz, Irwin R

2014-01-01

Healthcare safety and quality are critically important issues in obstetrics, and society, healthcare providers, patients and insurers share a common goal of working toward safer practice, and are continuously seeking strategies to facilitate improvements. To this end, 4 New York City voluntary hospitals with large maternity services initiated a unique collaborative quality improvement program. It was facilitated by their common risk management advisors, FOJP Service Corporation, and their professional liability insurer, Hospitals Insurance Company. Under the guidance of 4 obstetrics and gynecology departmental chairmen, consensus best practices for obstetrics were developed which included: implementation of evidence based protocols with audit and feedback; standardized educational interventions; mandatory electronic fetal monitoring training; and enhanced in-house physician coverage. Each institution developed unique safety related expertise (development of electronic documentation, team training, and simulation education), and experiences were shared across the collaborative. The collaborative group developed robust systems for audit of outcomes and documentation quality, as well as enforcement mechanisms. Ongoing feedback to providers served as a key component of the intervention. The liability carrier provided financial support for these patient safety innovations. As a result of the interventions, the overall AOI for our institutions decreased 42% from baseline (January-June 2008) to the most recently reviewed time period (July-December 2011) (10.7% vs 6.2%, p < 0.001). The Weighted Adverse Outcome Score (WAOS) also decreased during the same time period (3.9 vs 2.3, p = 0.001.) Given the improved outcomes noted, our unique program and the process by which it was developed are described in the hopes that others will recognize collaborative partnering with or without insurers as an opportunity to improve obstetric patient safety. © 2014 American Society for Healthcare Risk Management of the American Hospital Association.

The Genetic Interpretation of Area under the ROC Curve in Genomic Profiling

PubMed Central

Wray, Naomi R.; Yang, Jian; Goddard, Michael E.; Visscher, Peter M.

2010-01-01

Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease. The area under the receiver operator characteristic (ROC) curve is a well established measure for determining the efficacy of tests in correctly classifying diseased and non-diseased individuals. We use quantitative genetics theory to provide insight into the genetic interpretation of the area under the ROC curve (AUC) when the test classifier is a predictor of genetic risk. Even when the proportion of genetic variance explained by the test is 100%, there is a maximum value for AUC that depends on the genetic epidemiology of the disease, i.e. either the sibling recurrence risk or heritability and disease prevalence. We derive an equation relating maximum AUC to heritability and disease prevalence. The expression can be reversed to calculate the proportion of genetic variance explained given AUC, disease prevalence, and heritability. We use published estimates of disease prevalence and sibling recurrence risk for 17 complex genetic diseases to calculate the proportion of genetic variance that a test must explain to achieve AUC = 0.75; this varied from 0.10 to 0.74. We provide a genetic interpretation of AUC for use with predictors of genetic risk based on genomic profiles. We provide a strategy to estimate proportion of genetic variance explained on the liability scale from estimates of AUC, disease prevalence, and heritability (or sibling recurrence risk) available as an online calculator. PMID:20195508

Child-evoked maternal negativity from 9 to 27 months: evidence of gene-environment correlation and its moderation by marital distress

PubMed Central

Fearon, R.M. Pasco; Reiss, David; Leve, Leslie D.; Shaw, Daniel S.; Scaramella, Laura V.; Ganiban, Jody M.; Neiderhiser, Jenae M.

2014-01-01

Past research has documented pervasive genetic influences on emotional and behavioral disturbance across the lifespan and on liability to adult psychiatric disorder. Increasingly, interest is turning to mechanisms of gene-environment interplay in attempting to understand the earliest manifestations of genetic risk. We report findings from a prospective adoption study, which aimed to test the role of evocative gene-environment correlation in early development. 561 infants adopted at birth were studied between 9 and 27 months with their adoptive parents and birth mothers. Birth mother psychiatric diagnoses and symptoms scales were used as indicators of genetic influence, and multiple self-report measures were used to index adoptive mother parental negativity. We hypothesized that birth parent psychopathology would be associated with greater adoptive parent negativity, and that such evocative effects would be amplified under conditions of high family adversity. The findings suggested that genetic factors linked to birth mother externalizing psychopathology may evoke negative reactions in adoptive mothers in the first year of life, but primarily when the adoptive family environment was characterized by marital problems. The observed maternal negativity mediated the effects of genetic risk on child adjustment at 27 months. The results underline the importance of genetically-influenced evocative processes in early development. PMID:25216383

Child-evoked maternal negativity from 9 to 27 months: Evidence of gene-environment correlation and its moderation by marital distress.

PubMed

Fearon, R M Pasco; Reiss, David; Leve, Leslie D; Shaw, Daniel S; Scaramella, Laura V; Ganiban, Jody M; Neiderhiser, Jenae M

2015-11-01

Past research has documented pervasive genetic influences on emotional and behavioral disturbance across the life span and on liability to adult psychiatric disorder. Increasingly, interest is turning to mechanisms of gene-environment interplay in attempting to understand the earliest manifestations of genetic risk. We report findings from a prospective adoption study, which aimed to test the role of evocative gene-environment correlation in early development. Included in the study were 561 infants adopted at birth and studied between 9 and 27 months, along with their adoptive parents and birth mothers. Birth mother psychiatric diagnoses and symptoms scales were used as indicators of genetic influence, and multiple self-report measures were used to index adoptive mother parental negativity. We hypothesized that birth mother psychopathology would be associated with greater adoptive parent negativity and that such evocative effects would be amplified under conditions of high adoptive family adversity. The findings suggested that genetic factors associated with birth mother externalizing psychopathology may evoke negative reactions in adoptive mothers in the first year of life, but only when the adoptive family environment is characterized by marital problems. Maternal negativity mediated the effects of genetic risk on child adjustment at 27 months. The results underscore the importance of genetically influenced evocative processes in early development.

Oppositional Defiant Disorder dimensions: genetic influences and risk for later psychopathology

PubMed Central

Mikolajewski, Amy J.; Taylor, Jeanette; Iacono, William G.

2016-01-01

Background This study was undertaken to determine how well two Oppositional Defiant Disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Methods Psychopathology was assessed via diagnostic interviews of 1225 twin pairs at ages 11 and 17. Results Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior, and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Conclusions Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. PMID:28059443

Suicidal ideation, depression, and conduct disorder in a sample of adolescent and young adult twins

PubMed Central

Linker, Julie; Gillespie, Nathan A; Maes, Hermine; Eaves, Lindon; Silberg, Judy L.

2012-01-01

Background The co-occurrence of suicidal ideation, depression, and conduct disturbance is likely explained in part by correlated genetic and environmental risk factors. Little is known about the specific nature of these associations. Method Structured interviews on 2814 twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and young adult follow-up (YAFU) yielded data on symptoms of depression, conduct disorder and adolescent and young adult suicidal ideation. Results Univariate analyses revealed that the familial aggregation for each trait was explained by a combination of additive genetic and shared environmental effects. Suicidal ideation in adolescence was explained in part by genetic influences, but predominantly accounted for by environmental factors. A mixture of genetic and shared environmental influences explained ideation occurring in young adulthood. Multivariate analyses revealed that there are genetic and shared environmental effects common to suicidal ideation, depression, and conduct disorder. The association between adolescent suicidal ideation and CD was attributable to the same genetic and environmental risk factors for depression. Conclusions These findings underscore that prevention and intervention strategies should reflect the different underlying mechanisms involving depression and conduct disorder to assist in identifying adolescents at suicidal risk. PMID:22646517

Suicidal ideation, depression, and conduct disorder in a sample of adolescent and young adult twins.

PubMed

Linker, Julie; Gillespie, Nathan A; Maes, Hermine; Eaves, Lindon; Silberg, Judy L

2012-08-01

The co-occurrence of suicidal ideation, depression, and conduct disturbance is likely explained in part by correlated genetic and environmental risk factors. Little is known about the specific nature of these associations. Structured interviews on 2,814 twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU) yielded data on symptoms of depression, conduct disorder, and adolescent and young adult suicidal ideation. Univariate analyses revealed that the familial aggregation for each trait was explained by a combination of additive genetic and shared environmental effects. Suicidal ideation in adolescence was explained in part by genetic influences, but predominantly accounted for by environmental factors. A mixture of genetic and shared environmental influences explained ideation occurring in young adulthood. Multivariate analyses revealed that there are genetic and shared environmental effects common to suicidal ideation, depression, and conduct disorder. The association between adolescent suicidal ideation and CD was attributable to the same genetic and environmental risk factors for depression. These findings underscore that prevention and intervention strategies should reflect the different underlying mechanisms involving depression and conduct disorder to assist in identifying adolescents at suicidal risk. © 2012 The American Association of Suicidology.

Oppositional defiant disorder dimensions: genetic influences and risk for later psychopathology.

PubMed

Mikolajewski, Amy J; Taylor, Jeanette; Iacono, William G

2017-06-01

This study was undertaken to determine how well two oppositional defiant disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Psychopathology was assessed via diagnostic interviews of 1,225 twin pairs at ages 11 and 17. Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed that the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. © 2017 Association for Child and Adolescent Mental Health.

Genetic and environmental overlap between borderline personality disorder traits and psychopathy: evidence for promotive effects of factor 2 and protective effects of factor 1.

PubMed

Hunt, E; Bornovalova, M A; Patrick, C J

2015-05-01

Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies. The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs. Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses. These findings provide further insight into associations of psychopathic features - F1 as well as F2 - and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

Duty to disclose in medical genetics: a legal perspective.

PubMed

Pelias, M Z

1991-06-01

As technical knowledge and public information in medical genetics continue to expand, the geneticist may expect to be held responsible for informing patients and clients about new developments in research and diagnosis. The long legal evolution of the physician's duty to disclose, and more recent findings of a physician's duty to recall former patients to inform them about newly discovered risks of treatment, indicate that medical geneticists may have a duty to disclose both current and future information about conditions that are or could be inherited. Recent case law supports findings of professional liability for both present and future disclosure, even in the absence of an active physician-patient relationship. The requirement of candid and complete disclosure will affect the counseling approach in testing for deleterious genes and in providing medical treatment for minors with hereditary diseases. Finding a duty to recall may impose further professional burdens on the geneticist to reach beyond the immediate counseling arena and to recontact patients, perhaps years after their initial visit to genetics clinic.

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

PubMed Central

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G.; Nalls, Michael A.; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J.; Graff-Radford, Neill R.; Ross, Owen A.; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J.; Halliday, Glenda M.; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K.; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-01-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. PMID:26643944

Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR.

PubMed

Momeni, Stephanie S; Whiddon, Jennifer; Cheon, Kyounga; Ghazal, Tariq; Moser, Stephen A; Childers, Noel K

2016-09-01

This two-part study investigated the genetic diversity and transmission of Streptococcus mutans using the DiversiLab repetitive extragenic palindromic PCR (rep-PCR) approach. For children with S. mutans and participating household members, analysis for evidence of unrelated child-to-child as well as intra-familial transmission was evaluated based on commonality of genotypes. A total of 169 index children and 425 household family members from Uniontown, Alabama were evaluated for genetic diversity using rep-PCR. Thirty-four unique rep-PCR genotypes were observed for 13,906 S. mutans isolates. For transmission, 117 child and household isolates were evaluated for shared genotype (by child and by genotype cases, multiple matches possible for each child). Overall, children had 1-9 genotypes and those with multiple genotypes were 2.3 times more likely to have caries experience (decayed, missing and filled teeth/surfaces>0). Only 28% of children shared all genotypes within the household, while 72% had at least 1 genotype not shared with anyone in the household. Children had genotype(s) not shared with any household members in 157 cases. In 158 cases children and household members shared a genotype in which 55% (87/158 cases) were shared with more than one family member. Children most frequently shared genotypes with their mothers (54%; 85/158), siblings (46%; 72/158) and cousins (23%; 37/158). A reference library for S. mutans for epidemiological surveillance using the DiversiLab rep-PCR approach is detailed. The genetic diversity of S. mutans in this population demonstrated frequent commonality of genotypes. Evidence for both child-to-child and intra-familial transmission of S. mutans was observed by rep-PCR. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic Diversity and Evidence for Transmission of Streptococcus mutans by DiversiLab rep-PCR

PubMed Central

Momeni, Stephanie S.; Whiddon, Jennifer; Cheon, Kyounga; Ghazal, Tariq; Moser, Stephen A.; Childers, Noel K.

2016-01-01

This two-part study investigated the genetic diversity and transmission of Streptococcus mutans using the DiversiLab repetitive extragenic palindromic PCR (rep-PCR) approach. For children with S. mutans and participating household members, analysis for evidence of unrelated child-to-child as well as intra-familial transmission was evaluated based on commonality of genotypes. A total of 169 index children and 425 household family members from Uniontown, Alabama were evaluated for genetic diversity using rep-PCR. Thirty-four unique rep-PCR genotypes were observed for 13,906 S. mutans isolates. For transmission, 117 child and household isolates were evaluated for shared genotype (by child and by genotype cases, multiple matches possible for each child). Overall, children had 1–9 genotypes and those with multiple genotypes were 2.3 times more likely to have caries experience (decayed, missing and filled teeth/surfaces>0). Only 28% of children shared all genotypes within the household, while 72% had at least 1 genotype not shared with anyone in the household. Children had genotype(s) not shared with any household members in 155 cases. In 158 cases children and household members shared a genotype in which 55% (87/158 cases) were shared with more than one family member. Children most frequently shared genotypes with their mothers (54%; 85/158), siblings (46%; 72/158) and cousins (23%; 37/158). A reference library for S. mutans for epidemiological surveillance using the DiversiLab rep-PCR approach is detailed. The genetic diversity of S. mutans in this population demonstrated frequent commonality of genotypes. Evidence for both child-to-child and intra-familial transmission of S. mutans was observed by rep-PCR. PMID:27432341

75 FR 16645 - Increase in the Primary Nuclear Liability Insurance Premium

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-02

... Primary Nuclear Liability Insurance Premium AGENCY: Nuclear Regulatory Commission. ACTION: Final rule... impractical. The NRC is amending its regulations to increase the primary premium for liability insurance... protection requirements and indemnity agreements to increase the primary nuclear liability insurance layer...

Genetic Factors Influence Serological Measures of Common Infections

PubMed Central

Rubicz, Rohina; Leach, Charles T.; Kraig, Ellen; Dhurandhar, Nikhil V.; Duggirala, Ravindranath; Blangero, John; Yolken, Robert; Göring, Harald H.H.

2011-01-01

Background/Aims Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and −2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results Serological phenotypes were significantly heritable for most pathogens (h2 = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c2 = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance. PMID:21996708

Genetic specificity of face recognition.

PubMed

Shakeshaft, Nicholas G; Plomin, Robert

2015-10-13

Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

Genetic specificity of face recognition

PubMed Central

Shakeshaft, Nicholas G.; Plomin, Robert

2015-01-01

Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities. PMID:26417086

Shared Genetic Aetiology between Cognitive Ability and Cardiovascular Disease Risk Factors: Generation Scotland's Scottish Family Health Study

ERIC Educational Resources Information Center

Luciano, Michelle; Batty, G. David; McGilchrist, Mark; Linksted, Pamela; Fitzpatrick, Bridie; Jackson, Cathy; Pattie, Alison; Dominiczak, Anna F.; Morris, Andrew D.; Smith, Blair H.; Porteous, David; Deary, Ian J.

2010-01-01

People with higher general cognitive ability in early life have more favourable levels of cardiovascular disease (CVD) risk factors in adulthood and CVD itself. The mechanism of these associations is not known. Here we examine whether general cognitive ability and CVD risk factors share genetic and/or environmental aetiology. In this large,…

Literacy outcomes of children with early childhood speech sound disorders: impact of endophenotypes.

PubMed

Lewis, Barbara A; Avrich, Allison A; Freebairn, Lisa A; Hansen, Amy J; Sucheston, Lara E; Kuo, Iris; Taylor, H Gerry; Iyengar, Sudha K; Stein, Catherine M

2011-12-01

To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Children with SSD and their siblings were assessed at early childhood (ages 4-6 years) and followed at school age (7-12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills.

Literacy Outcomes of Children With Early Childhood Speech Sound Disorders: Impact of Endophenotypes

PubMed Central

Lewis, Barbara A.; Avrich, Allison A.; Freebairn, Lisa A.; Hansen, Amy J.; Sucheston, Lara E.; Kuo, Iris; Taylor, H. Gerry; Iyengar, Sudha K.; Stein, Catherine M.

2012-01-01

Purpose To demonstrate that early childhood speech sound disorders (SSD) and later school-age reading, written expression, and spelling skills are influenced by shared endophenotypes that may be in part genetic. Method Children with SSD and their siblings were assessed at early childhood (ages 4–6 years) and followed at school age (7–12 years). The relationship of shared endophenotypes with early childhood SSD and school-age outcomes and the shared genetic influences on these outcomes were examined. Results Structural equation modeling demonstrated that oral motor skills, phonological awareness, phonological memory, vocabulary, and speeded naming have varying influences on reading decoding, spelling, spoken language, and written expression at school age. Genetic linkage studies demonstrated linkage for reading, spelling, and written expression measures to regions on chromosomes 1, 3, 6, and 15 that were previously linked to oral motor skills, articulation, phonological memory, and vocabulary at early childhood testing. Conclusions Endophenotypes predict school-age literacy outcomes over and above that predicted by clinical diagnoses of SSD or language impairment. Findings suggest that these shared endophenotypes and common genetic influences affect early childhood SSD and later school-age reading, spelling, spoken language, and written expression skills. PMID:21930616

Genetics of Attention Deficit Hyperactivity Disorder: A Current Review and Future Prospects

ERIC Educational Resources Information Center

Levy, Florence; Hay, David A.; Bennett, Kellie S.

2006-01-01

While there have been significant advances in both the behaviour genetics and molecular genetics of Attention Deficit Hyperactivity Disorder (ADHD), researchers are now beginning to develop hypotheses about relationships between phenotypes and genetic mechanisms. Twin studies are able to model genetic, shared environmental and non-shared…

The preclinical testing strategy for the development of novel chemical entities for the treatment of asthma.

PubMed

Hahn, Christian; Erb, Klaus Joseph

2008-06-01

Identifying and developing novel chemical entities (NCE) for the treatment of asthma is a time-consuming process and liabilities that endanger the successful progression of a compound from research into the patient are found throughout all phases of drug discovery. In particular the failure of advanced compounds in clinical studies due to lack of efficacy and/or safety concerns is tremendously costly. Therefore, in order to try and reduce the failure rate in clinical trials various in vitro and in vivo tests are performed during preclinical development, to rapidly identify liabilities, eliminate high risk compounds and promote promising potential drug candidates. To achieve this objective, numerous prerequisites have to be met regarding the physico-chemical properties of the compound, and bioactivity or model systems are needed to rate the therapeutic potential of new compounds. Drug liabilities such as target and species specificity, formulation issues, pharmacokinetics as well as pharmacodynamics and the toxic potential of the compound have to be analyzed in great detail before a compound can enter a clinical trial. A particularly challenging aspect of developing novel NCEs for the treatment of asthma is choosing and setting up in vivo models believed to be predictive for human disease. Numerous companies have in the past and are currently developing NCEs targeting many different pathways and cells with the aim to treat asthma. However, currently the only NCE having a significant market share are long-acting beta-agonists (LABA), inhaled and orally active steroids and leukotriene receptor antagonists. In the past many novel NCE for the treatment of asthma were effective in animal models but failed in the clinic. In this review we outline the prerequisites of novel NCE needed for clinical development.

26 CFR 1.704-2 - Allocations attributable to nonrecourse liabilities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... disparity. (4) Special rule for year of revaluation. (e) Requirements to be satisfied. (f) Minimum gain... encumbers, a disposition of that property will generate gain that at least equals that excess (“partnership.... (3) Definition of nonrecourse liability. Nonrecourse liability means a nonrecourse liability as...

14 CFR 291.22 - Aircraft accident liability insurance requirement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Aircraft accident liability insurance... for All-Cargo Air Transportation § 291.22 Aircraft accident liability insurance requirement. No air... and maintains in effect aircraft accident liability coverage that meets the requirements of part 205...

46 CFR 5.69 - Evidence of criminal liability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... INVESTIGATION REGULATIONS-PERSONNEL ACTION Statement of Policy and Interpretation § 5.69 Evidence of criminal liability. Evidence of criminal liability discovered during an investigation or hearing conducted pursuant... 46 Shipping 1 2010-10-01 2010-10-01 false Evidence of criminal liability. 5.69 Section 5.69...

14 CFR 1260.61 - Allocation of risk/liability.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Allocation of risk/liability. 1260.61 Section 1260.61 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.61 Allocation of risk/liability. Allocation of Risk/Liability...

Admixture into and within sub-Saharan Africa

PubMed Central

Busby, George BJ; Band, Gavin; Si Le, Quang; Jallow, Muminatou; Bougama, Edith; Mangano, Valentina D; Amenga-Etego, Lucas N; Enimil, Anthony; Apinjoh, Tobias; Ndila, Carolyne M; Manjurano, Alphaxard; Nyirongo, Vysaul; Doumba, Ogobara; Rockett, Kirk A; Kwiatkowski, Dominic P; Spencer, Chris CA

2016-01-01

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology. DOI: http://dx.doi.org/10.7554/eLife.15266.001 PMID:27324836

Heuristic Identification of Biological Architectures for Simulating Complex Hierarchical Genetic Interactions

PubMed Central

Moore, Jason H; Amos, Ryan; Kiralis, Jeff; Andrews, Peter C

2015-01-01

Simulation plays an essential role in the development of new computational and statistical methods for the genetic analysis of complex traits. Most simulations start with a statistical model using methods such as linear or logistic regression that specify the relationship between genotype and phenotype. This is appealing due to its simplicity and because these statistical methods are commonly used in genetic analysis. It is our working hypothesis that simulations need to move beyond simple statistical models to more realistically represent the biological complexity of genetic architecture. The goal of the present study was to develop a prototype genotype–phenotype simulation method and software that are capable of simulating complex genetic effects within the context of a hierarchical biology-based framework. Specifically, our goal is to simulate multilocus epistasis or gene–gene interaction where the genetic variants are organized within the framework of one or more genes, their regulatory regions and other regulatory loci. We introduce here the Heuristic Identification of Biological Architectures for simulating Complex Hierarchical Interactions (HIBACHI) method and prototype software for simulating data in this manner. This approach combines a biological hierarchy, a flexible mathematical framework, a liability threshold model for defining disease endpoints, and a heuristic search strategy for identifying high-order epistatic models of disease susceptibility. We provide several simulation examples using genetic models exhibiting independent main effects and three-way epistatic effects. PMID:25395175

Childhood and adolescent anxiety and depression: beyond heritability.

PubMed

Franić, Sanja; Middeldorp, Christel M; Dolan, Conor V; Ligthart, Lannie; Boomsma, Dorret I

2010-08-01

To review the methodology of behavior genetics studies addressing research questions that go beyond simple heritability estimation and illustrate these using representative research on childhood and adolescent anxiety and depression. The classic twin design and its extensions may be used to examine age and gender differences in the genetic determinants of complex traits and disorders, the role of genetic factors in explaining comorbidity, the interaction of genes and the environment, and the effect of social interaction among family members. An overview of the methods typically employed to address such questions is illustrated by a review of 34 recent studies on childhood anxiety and depression. The review provides relatively consistent evidence for small to negligible sex differences in the genetic etiology of childhood anxiety and depression, a substantial role of genetic factors in accounting for the temporal stability of these disorders, a partly genetic basis of the comorbidity between anxiety and depression, a possible role of the interaction between genotype and the environment in affecting liability to these disorders, a role of genotype-environment correlation, and a minor, if any, etiological role of sibling interaction. The results clearly demonstrate a role for genetic factors in the etiology and temporal stability of individual differences in childhood anxiety and depression. Clinical implications of the findings are discussed. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Insurance and indemnification implications of future space projects

NASA Technical Reports Server (NTRS)

O'Brien, John E.

1987-01-01

NASA options regarding insurance and indemnification policies as they relate to NASA customers and contractors are described. The foundation for the discussion is the way in which NASA is planning to return the Space Shuttle fleet to safe flight as well as current U.S. policy concerning future uses of the Shuttle fleet. Issues discussed include: the nature of the Shuttle manifest; the policy regarding property damage or destruction; insurance against liability to third parties; the reduction of the scope of the risk to be insured; NASA as the insurer; a sharing arrangement between the user and NASA; and contractors and subcontractors involved in Shuttle operations.

PLASMA LIPIDOMIC PROFILE SIGNATURE OF HYPERTENSION IN MEXICAN AMERICAN FAMILIES: SPECIFIC ROLE OF DIACYLGLYCEROLS

PubMed Central

Kulkarni, Hemant; Meikle, Peter J.; Mamtani, Manju; Weir, Jacquelyn M.; Barlow, Christopher K.; Jowett, Jeremy B.; Bellis, Claire; Dyer, Thomas D.; Johnson, Matthew P.; Rainwater, David L.; Almasy, Laura; Mahaney, Michael C.; Commuzzie, Anthony G.; Blangero, John; Curran, Joanne E.

2013-01-01

Both as a component of metabolic syndrome and as an independent entity, hypertension poses a continued challenge with regard to its diagnosis, pathogenesis and treatment. Previous studies have documented connections between hypertension and indicators of lipid metabolism. Novel technologies like plasma lipidomic profiling promise a better understanding of disorders in which there is a derangement of the lipid metabolism. However, association of plasma lipidomic profiles with hypertension in a high-risk population, like Mexican Americans, has not been evaluated before. Using the rich data and sample resource from the ongoing San Antonio Family Heart Study, we conducted plasma lipidomic profiling by combining high performance liquid chromatography with tandem mass spectroscopy to characterize 319 lipid species in 1192 individuals from 42 large and extended Mexican American families. Robust statistical analyses employing polygenic regression models, liability threshold models and bivariate trait analyses implemented in the SOLAR software were conducted after accounting for obesity, insulin resistance and relative abundance of various lipoprotein fractions. Diacylglycerols in general and the DG 16:0/22:5 and DG 16:0/22:6 lipid species in particular were significantly associated with systolic, diastolic and mean arterial pressures as well as liability of incident hypertension measured during 7767.42 person-years of follow-up. Four lipid species, including the DG 16:0/22:5 and DG 16:0/22:6 species, showed significant genetic correlations with the liability of hypertension in bivariate trait analyses. Our results demonstrate the value of plasma lipidomic profiling in the context of hypertension and identify disturbance of diacyglycerol metabolism as an independent biomarker of hypertension. PMID:23798346

Perspective on a Modified Developmental and Reproductive Toxicity Testing Strategy for Cancer Immunotherapy.

PubMed

Prell, Rodney A; Halpern, Wendy G; Rao, Gautham K

2016-05-01

The intent of cancer immunotherapy (CIT) is to generate and enhance T-cell responses against tumors. The tumor microenvironment establishes several inhibitory pathways that lead to suppression of the local immune response, which is permissive for tumor growth. The efficacy of different CITs, alone and in combination, stems from reinvigorating the tumor immune response via several mechanisms, including costimulatory agonists, checkpoint inhibitors, and vaccines. However, immune responses to other antigens (self and foreign) may also be enhanced, resulting in potentially undesired effects. In outbred mammalian pregnancies, the fetus expresses paternally derived alloantigens that are recognized as foreign by the maternal immune system. If unchecked or enhanced, maternal immunity to these alloantigens represents a developmental and reproductive risk and thus is a general liability for cancer immunotherapeutic molecules. We propose a tiered approach to confirm this mechanistic reproductive liability for CIT molecules. A rodent allopregnancy model is based on breeding 2 different strains of mice so that paternally derived alloantigens are expressed by the fetus. When tested with a cross-reactive biotherapeutic, small molecule drug, or surrogate molecule, this model should reveal on-target reproductive liabilities if the pathway is involved in maintaining pregnancy. Alternatively, allopregnancy models with genetically modified mice can be interrogated for exquisitely specific biotherapeutics with restricted species reactivity. The allopregnancy model represents a relatively straightforward approach to confirm an expected on-target reproductive risk for CIT molecules. For biotherapeutics, it could potentially replace more complex developmental and reproductive toxicity testing in nonhuman primates when a pregnancy hazard is confirmed or expected. © The Author(s) 2016.

Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared Middle Eastern Ancestry.

PubMed

Atzmon, Gil; Hao, Li; Pe'er, Itsik; Velez, Christopher; Pearlman, Alexander; Palamara, Pier Francesco; Morrow, Bernice; Friedman, Eitan; Oddoux, Carole; Burns, Edward; Ostrer, Harry

2010-06-11

For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15th century to 5,000,000 people at the beginning of the 19th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads.

Abraham's Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry

PubMed Central

Atzmon, Gil; Hao, Li; Pe'er, Itsik; Velez, Christopher; Pearlman, Alexander; Palamara, Pier Francesco; Morrow, Bernice; Friedman, Eitan; Oddoux, Carole; Burns, Edward; Ostrer, Harry

2010-01-01

For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15th century to 5,000,000 people at the beginning of the 19th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads. PMID:20560205

Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.

PubMed

Smeland, Olav B; Frei, Oleksandr; Kauppi, Karolina; Hill, W David; Li, Wen; Wang, Yunpeng; Krull, Florian; Bettella, Francesco; Eriksen, Jon A; Witoelar, Aree; Davies, Gail; Fan, Chun C; Thompson, Wesley K; Lam, Max; Lencz, Todd; Chen, Chi-Hua; Ueland, Torill; Jönsson, Erik G; Djurovic, Srdjan; Deary, Ian J; Dale, Anders M; Andreassen, Ole A

2017-10-01

Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10-7), general cognitive function (z score, -4.43; P = 9.42 × 10-6), and verbal-numerical reasoning (z score, -5.43; P = 5.64 × 10-8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

An 8-Year Breeding Program for Asian Seabass Lates calcarifer: Genetic Evaluation, Experiences, and Challenges.

PubMed

Khang, Pham Van; Phuong, Truong Ha; Dat, Nguyen Khac; Knibb, Wayne; Nguyen, Nguyen Hong

2018-01-01

Selective breeding for marine finfish is challenging due to difficulties in reproduction, larval rearing, and on-growth in captive environments. The farming of Asian seabass ( Lates calcarifer ) has all these problems and our knowledge of the quantitative genetic information (heritability and correlations) of traits necessary for commercial exploitation is poor. The present study was conducted to address this knowledge gap and to provide information that can be applied to sea bass and other aquaculture species. We carried out a comprehensive genetic evaluation for three traits (body weight, total length, and survival) collected from a breeding population for Asian seabass over an eight-year period from 2010 to 2017. Statistical analysis was carried out on 4,567 adult fish at 105, 180, 270, 360, 450, and 570 days post-hatch (dph). The heritabilities (h 2 ) estimated for body weight and length using linear mixed model were moderate to high (0.12 to 0.78 and 0.41 to 0.85, respectively) and they differed between the measurement periods. Survival during grow-out phase was analyzed using threshold logistic and probit models. The heritability estimates for survival rate on the underlying liability scale ( h L 2 ) varied from 0.05 to 0.21. When the observed heritability obtained from the linear mixed model was back-transformed to the liability scale, they were similar but not significant. In addition, we examined effects of genotype by environment (G × E) interaction on body traits. The genetic correlation for body weight between tank and sea cage cultures were high (0.91-0.94) in the first and second rearing periods (180 and 270 dph) but the correlation was decreased to 0.59 ± 0.33 at 360 dph. This suggests that the genotype by environment interaction is important for body traits in this population. Furthermore, the genetic correlations of body weights between different measurement periods were moderate but different from one. This suggests that body weights measured at different time points may be different traits and selection for improved early weight may not capture all genetic expressions in subsequent rearing periods in Asian seabass. Selection of the nucleus in sea cages may produce genotypes that do not perform equally well in tanks, although this deserves further studies to determine a suitable selection environment and optimize the breeding program. This paper discusses challenges encountered during implementation of the selection program for L. calcarifer .

12 CFR 965.2 - Authorized liabilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Authorized liabilities. 965.2 Section 965.2 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK LIABILITIES SOURCE OF FUNDS § 965.2 Authorized liabilities. As a source of funds for business operations, each Bank is authorized to...

12 CFR 704.8 - Asset and liability management.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CORPORATE CREDIT UNIONS § 704.8 Asset and liability management. (a) Policies. A corporate credit union must...) The purpose and objectives of the corporate credit union's asset and liability activities; (2) The... used as a basis of estimation. (b) Asset and liability management committee (ALCO). A corporate credit...

12 CFR 704.8 - Asset and liability management.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CORPORATE CREDIT UNIONS § 704.8 Asset and liability management. (a) Policies. A corporate credit union must...) The purpose and objectives of the corporate credit union's asset and liability activities; (2) The... used as a basis of estimation. (b) Asset and liability management committee (ALCO). A corporate credit...

14 CFR 1274.916 - Liability and risk of loss.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Liability and risk of loss. 1274.916... AGREEMENTS WITH COMMERCIAL FIRMS Other Provisions and Special Conditions § 1274.916 Liability and risk of..., or indemnification of, developers of experimental aerospace vehicles. Liability and Risk of Loss July...

12 CFR 229.21 - Civil liability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 3 2014-01-01 2014-01-01 false Civil liability. 229.21 Section 229.21 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM... Disclosure of Funds Availability Policies § 229.21 Civil liability. (a) Civil liability. A bank that fails to...

12 CFR 229.21 - Civil liability.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Civil liability. 229.21 Section 229.21 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM... Availability Policies § 229.21 Civil liability. (a) Civil liability. A bank that fails to comply with any...

12 CFR 229.21 - Civil liability.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 3 2012-01-01 2012-01-01 false Civil liability. 229.21 Section 229.21 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM... Availability Policies § 229.21 Civil liability. (a) Civil liability. A bank that fails to comply with any...

12 CFR 229.21 - Civil liability.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Civil liability. 229.21 Section 229.21 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM... Availability Policies § 229.21 Civil liability. (a) Civil liability. A bank that fails to comply with any...

12 CFR 229.21 - Civil liability.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 3 2013-01-01 2013-01-01 false Civil liability. 229.21 Section 229.21 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM... Disclosure of Funds Availability Policies § 229.21 Civil liability. (a) Civil liability. A bank that fails to...

Alcohol use disorder and divorce: evidence for a genetic correlation in a population-based Swedish sample.

PubMed

Salvatore, Jessica E; Larsson Lönn, Sara; Sundquist, Jan; Lichtenstein, Paul; Sundquist, Kristina; Kendler, Kenneth S

2017-04-01

We tested the association between alcohol use disorder (AUD) and divorce; estimated the genetic and environmental influences on divorce; estimated how much genetic and environmental influences accounted for covariance between AUD and divorce; and estimated latent genetic and environmental correlations between AUD and divorce. We tested sex differences in these effects. We identified twin and sibling pairs with AUD and divorce information in Swedish national registers. We described the association between AUD and divorce using tetrachorics and used twin and sibling models to estimate genetic and environmental influences on divorce, on the covariance between AUD and divorce and the latent genetic and environmental correlations between AUD and divorce. Sweden. A total of 670 836 individuals (53% male) born 1940-1965. Life-time measures of AUD and divorce. AUD and divorce were related strongly (males: r tet  = +0.44, 95% CI = 0.43, 0.45; females r tet  = +0.37, 95% CI = 0.36, 0.38). Genetic factors accounted for a modest proportion of the variance in divorce (males: 21.3%, 95% CI = 7.6, 28.5; females: 31.0%, 95% CI = 18.8, 37.1). Genetic factors accounted for most of the covariance between AUD and divorce (males: 52.0%, 95% CI = 48.8, 67.9; females: 53.74%, 95% CI = 17.6, 54.5), followed by non-shared environmental factors (males: 45.0%, 95% CI = 37.5, 54.9; females: 41.6%, 95% CI = 40.3, 60.2). Shared environmental factors accounted for a negligible proportion of the covariance (males: 3.0%, 95% CI = -3.0, 13.5; females: 4.75%, 95% CI = 0.0, 6.6). The AUD-divorce genetic correlations were high (males: rA = +0.76, 95% CI = 0.53, 0.90; females +0.52, 95% CI = 0.24, 0.67). The non-shared environmental correlations were modest (males: rE = +0.32, 95% CI = 0.31, 0.40; females: +0.27, 95% CI = 0.27, 0.36). Divorce and alcohol use disorder are correlated strongly in the Swedish population, and the heritability of divorce is consistent with previous studies. Covariation between AUD and divorce results from overlapping genetic and non-shared environmental factors. Latent genetic and non-shared environmental correlations for alcohol use disorder and divorce are high and moderate. © 2016 Society for the Study of Addiction.

The genetic relationship between cannabis and tobacco cigarette use in European- and African-American female twins and siblings.

PubMed

Agrawal, Arpana; Grant, Julia D; Lynskey, Michael T; Madden, Pamela A F; Heath, Andrew C; Bucholz, Kathleen K; Sartor, Carolyn E

2016-06-01

Use of cigarettes and cannabis frequently co-occurs. We examine the role of genetic and environmental influences on variation in and covariation between tobacco cigarette and cannabis use across European-American (EA) and African-American (AA) women. Data on lifetime cannabis and cigarette use were drawn from interviews of 956 AA and 3557 EA young adult female twins and non-twin same sex female full siblings. Twin modeling was used to decompose variance in and covariance between cigarette and cannabis use into additive genetic, shared, special twin and non-shared environmental sources. Cigarette use was more common in EAs (75.3%, 95% C.I. 73.8-76.7%) than AAs (64.2%, 95% C.I. 61.2-67.2%) while cannabis use was marginally more commonly reported by AAs (55.5%, 95% C.I. 52.5-58.8%) than EAs (52.4%, 95% C.I. 50.7-54.0%). Additive genetic factors were responsible for 43-66% of the variance in cigarette and cannabis use. Broad shared environmental factors (shared+special twin) played a more significant role in EA (23-29%) than AA (2-15%) women. In AA women, the influence of non-shared environment was more pronounced (42-45% vs. 11-19% in EA women). There was strong evidence for the same familial influences underlying use of both substances (rA=0.82-0.89; rC+T=0.70-0.75). Non-shared environmental factors were also correlated but less so (rE=0.48-0.66). No racial/ethnic differences were apparent in these sources of covariation. Heritability of cigarette and cannabis use is comparable across racial/ethnic groups. Differences in the contribution of shared and non-shared environmental influences indicate that different factors may shape substance use in EA and AA women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Understanding alcohol use disorders with neuroelectrophysiology

PubMed Central

RANGASWAMY, MADHAVI; PORJESZ, BERNICE

2015-01-01

Neurocognitive deficits associated with impairments in various brain regions and neural circuitries, particularly involving frontal lobes, have been associated with chronic alcoholism, as well as with a predisposition to develop alcohol use and related disorders (AUDs). AUD is a multifactorial disorder caused by complex interactions between behavioral, genetic, and environmental liabilities. Neuroelectrophysiological techniques are instrumental in understanding brain and behavior relationships and have also proved very useful in evaluating the genetic diathesis of alcoholism. This chapter describes findings from neuroelectrophysiological measures (electroencephalogram, event-related potentials, and event-related oscillations) related to acute and chronic effects of alcohol on the brain and those that reflect underlying deficits related to a predisposition to develop AUDs and related disorders. The utility of these measures as effective endophenotypes to identify and understand genes associated with brain electrophysiology, cognitive networks, and AUDs has also been discussed. PMID:25307587

78 FR 13286 - Sharing Certain Business Information Regarding the Introduction of Genetically Engineered...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... Information Regarding the Introduction of Genetically Engineered Organisms With State and Tribal Government... proposing to amend our regulations regarding genetically engineered organisms regulated by the United States...). The regulations refer to such genetically engineered (GE) organisms and products as ``regulated...

Bartonellae are Prevalent and Diverse in Costa Rican Bats and Bat Flies.

PubMed

Judson, S D; Frank, H K; Hadly, E A

2015-12-01

Species in the bacterial genus, Bartonella, can cause disease in both humans and animals. Previous reports of Bartonella in bats and ectoparasitic bat flies suggest that bats could serve as mammalian hosts and bat flies as arthropod vectors. We compared the prevalence and genetic similarity of bartonellae in individual Costa Rican bats and their bat flies using molecular and sequencing methods targeting the citrate synthase gene (gltA). Bartonellae were more prevalent in bat flies than in bats, and genetic variants were sometimes, but not always, shared between bats and their bat flies. The detected bartonellae genetic variants were diverse, and some were similar to species known to cause disease in humans and other mammals. The high prevalence and sharing of bartonellae in bat flies and bats support a role for bat flies as a potential vector for Bartonella, while the genetic diversity and similarity to known species suggest that bartonellae could spill over into humans and animals sharing the landscape. © 2015 Blackwell Verlag GmbH.

Has the "Equal Environments" assumption been tested in twin studies?

PubMed

Eaves, Lindon; Foley, Debra; Silberg, Judy

2003-12-01

A recurring criticism of the twin method for quantifying genetic and environmental components of human differences is the necessity of the so-called "equal environments assumption" (EEA) (i.e., that monozygotic and dizygotic twins experience equally correlated environments). It has been proposed to test the EEA by stratifying twin correlations by indices of the amount of shared environment. However, relevant environments may also be influenced by genetic differences. We present a model for the role of genetic factors in niche selection by twins that may account for variation in indices of the shared twin environment (e.g., contact between members of twin pairs). Simulations reveal that stratification of twin correlations by amount of contact can yield spurious evidence of large shared environmental effects in some strata and even give false indications of genotype x environment interaction. The stratification approach to testing the equal environments assumption may be misleading and the results of such tests may actually be consistent with a simpler theory of the role of genetic factors in niche selection.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations.

PubMed

Kopelman, Naama M; Stone, Lewi; Wang, Chaolong; Gefel, Dov; Feldman, Marcus W; Hillel, Jossi; Rosenberg, Noah A

2009-12-08

Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations

PubMed Central

2009-01-01

Background Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. Results We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. Conclusion These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent. PMID:19995433

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

PubMed Central

Burri, Andrea; Cherkas, Lynn; Spector, Timothy; Rahman, Qazi

2011-01-01

Background Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation. PMID:21760939

Redefining genomic privacy: trust and empowerment.

PubMed

Erlich, Yaniv; Williams, James B; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D; Witkowski, Jan A; Kain, Robert C

2014-11-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research.

Examining the genetic and environmental associations among spelling, reading fluency, reading comprehension and a high stakes reading test in a combined sample of third and fourth grade students

PubMed Central

Little, Callie W.

2015-01-01

The present study is an examination of the genetic and environmental effects on the associations among reading fluency, spelling and earlier reading comprehension on a later reading comprehension outcome (FCAT) in a combined sample of 3rd and 4th grade students using data from the 2011-2012 school year of the Florida Twin project on Reading (Taylor et al., 2013). A genetically sensitive model was applied to the data with results indicating a common genetic component among all four measures, along with shared and non-shared environmental influences common between reading fluency, spelling and FCAT. PMID:26770052

Redefining Genomic Privacy: Trust and Empowerment

PubMed Central

Erlich, Yaniv; Williams, James B.; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D.; Witkowski, Jan A.; Kain, Robert C.

2014-01-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research. PMID:25369215

Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.

PubMed

Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J; Graff-Radford, Neill R; Ross, Owen A; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J; Halliday, Glenda M; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

2016-02-01

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The U.S. Culture Collection Network Responding to the Requirements of the Nagoya Protocol on Access and Benefit Sharing

PubMed Central

Barker, Katharine B.; Barton, Hazel A.; Boundy-Mills, Kyria; Brown, Daniel R.; Coddington, Jonathan A.; Cook, Kevin; Desmeth, Philippe; Geiser, David; Glaeser, Jessie A.; Greene, Stephanie; Kang, Seogchan; Lomas, Michael W.; Melcher, Ulrich; Miller, Scott E.; Nobles, David R.; Owens, Kristina J.; Reichman, Jerome H.; da Silva, Manuela; Wertz, John; Whitworth, Cale; Smith, David

2017-01-01

ABSTRACT The U.S. Culture Collection Network held a meeting to share information about how culture collections are responding to the requirements of the recently enacted Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity (CBD). The meeting included representatives of many culture collections and other biological collections, the U.S. Department of State, U.S. Department of Agriculture, Secretariat of the CBD, interested scientific societies, and collection groups, including Scientific Collections International and the Global Genome Biodiversity Network. The participants learned about the policies of the United States and other countries regarding access to genetic resources, the definition of genetic resources, and the status of historical materials and genetic sequence information. Key topics included what constitutes access and how the CBD Access and Benefit-Sharing Clearing-House can help guide researchers through the process of obtaining Prior Informed Consent on Mutually Agreed Terms. U.S. scientists and their international collaborators are required to follow the regulations of other countries when working with microbes originally isolated outside the United States, and the local regulations required by the Nagoya Protocol vary by the country of origin of the genetic resource. Managers of diverse living collections in the United States described their holdings and their efforts to provide access to genetic resources. This meeting laid the foundation for cooperation in establishing a set of standard operating procedures for U.S. and international culture collections in response to the Nagoya Protocol. PMID:28811341