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Sample records for african ancestry individuals

  1. Replication and fine mapping of asthma-associated loci in individuals of African ancestry.

    PubMed

    Kantor, David B; Palmer, Cameron D; Young, Taylor R; Meng, Yan; Gajdos, Zofia K; Lyon, Helen; Price, Alkes L; Pollack, Samuela; London, Stephanie J; Loehr, Laura R; Smith, Lewis J; Kumar, Rajesh; Jacobs, David R; Petrini, Marcy F; O'Connor, George T; White, Wendy B; Papanicolaou, George; Burkart, Kristin M; Heckbert, Susan R; Barr, R Graham; Hirschhorn, Joel N

    2013-09-01

    Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.

  2. Importance of mitochondrial haplotypes and maternal lineage in sprint performance among individuals of West African ancestry.

    PubMed

    Deason, M; Scott, R; Irwin, L; Macaulay, V; Fuku, N; Tanaka, M; Irving, R; Charlton, V; Morrison, E; Austin, K; Pitsiladis, Y P

    2012-04-01

    Mitochondrial DNA (mtDNA) is inherited solely along the matriline, giving insight into both ancestry and prehistory. Individuals of sub-Saharan ancestry are overrepresented in sprint athletics, suggesting a genetic advantage. The purpose of this study was to compare the mtDNA haplogroup data of elite groups of Jamaican and African-American sprinters against respective controls to assess any differences in maternal lineage. The first hypervariable region of mtDNA was haplogrouped in elite Jamaican athletes (N=107) and Jamaican controls (N=293), and elite African-American athletes (N=119) and African-American controls (N=1148). Exact tests of total population differentiation were performed on total haplogroup frequencies. The frequency of non-sub-Saharan haplogroups in Jamaican athletes and Jamaican controls was similar (1.87% and 1.71%, respectively) and lower than that of African-American athletes and African-American controls (21.01% and 8.19%, respectively). There was no significant difference in total haplogroup frequencies between Jamaican athletes and Jamaican controls (P=0.551 ± 0.005); however, there was a highly significant difference between African-American athletes and African-American controls (P<0.001). The finding of statistically similar mtDNA haplogroup distributions in Jamaican athletes and Jamaican controls suggests that elite Jamaican sprinters are derived from the same source population and there is neither population stratification nor isolation for sprint performance. The significant difference between African-American sprinters and African-American controls suggests that the maternal admixture may play a role in sprint performance.

  3. Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

    PubMed Central

    Ge, Bing; Tayo, Bamidele; Mathias, Rasika A.; Ding, Jingzhong; Nalls, Michael A.; Adeyemo, Adebowale; Adoue, Véronique; Ambrosone, Christine B.; Atwood, Larry; Bandera, Elisa V.; Becker, Lewis C.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Boerwinkle, Eric; Britton, Angela; Casey, Graham; Chanock, Stephen J.; Demerath, Ellen; Deming, Sandra L.; Diver, W. Ryan; Fox, Caroline; Harris, Tamara B.; Hernandez, Dena G.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Johnson, Craig; Keating, Brendan; Kittles, Rick A.; Kolonel, Laurence N.; Kritchevsky, Stephen B.; Le Marchand, Loic; Lohman, Kurt; Liu, Jiankang; Millikan, Robert C.; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; North, Kari E.; Nyante, Sarah; Ogunniyi, Adesola; Ostrander, Elaine A.; Papanicolaou, George; Patel, Sanjay; Pettaway, Curtis A.; Press, Michael F.; Redline, Susan; Rodriguez-Gil, Jorge L.; Rotimi, Charles; Rybicki, Benjamin A.; Salako, Babatunde; Schreiner, Pamela J.; Signorello, Lisa B.; Singleton, Andrew B.; Stanford, Janet L.; Stram, Alex H.; Stram, Daniel O.; Strom, Sara S.; Suktitipat, Bhoom; Thun, Michael J.; Witte, John S.; Yanek, Lisa R.; Ziegler, Regina G.; Zheng, Wei; Zhu, Xiaofeng; Zmuda, Joseph M.; Zonderman, Alan B.; Evans, Michele K.; Liu, Yongmei; Becker, Diane M.; Cooper, Richard S.; Pastinen, Tomi; Henderson, Brian E.; Hirschhorn, Joel N.; Lettre, Guillaume; Haiman, Christopher A.

    2011-01-01

    Adult height is a classic polygenic trait of high heritability (h 2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits. PMID:21998595

  4. Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study

    PubMed Central

    Bidulescu, Aurelian; Choudhry, Shweta; Musani, Solomon K.; Buxbaum, Sarah G.; Liu, Jiankang; Rotimi, Charles N.; Wilson, James G.; Taylor, Herman A.; Gibbons, Gary H.

    2014-01-01

    Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (β = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; β = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels. PMID:24575123

  5. IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry

    PubMed Central

    Sanabria-Salas, María Carolina; Hernández-Suárez, Gustavo; Umaña-Pérez, Adriana; Rawlik, Konrad; Tenesa, Albert; Serrano-López, Martha Lucía; Sánchez de Gómez, Myriam; Rojas, Martha Patricia; Bravo, Luis Eduardo; Albis, Rosario; Plata, José Luis; Green, Heather; Borgovan, Theodor; Li, Li; Majumdar, Sumana; Garai, Jone; Lee, Edward; Ashktorab, Hassan; Brim, Hassan; Li, Li; Margolin, David; Fejerman, Laura; Zabaleta, Jovanny

    2017-01-01

    Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31–3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk. PMID:28157220

  6. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.

    PubMed

    Monda, Keri L; Chen, Gary K; Taylor, Kira C; Palmer, Cameron; Edwards, Todd L; Lange, Leslie A; Ng, Maggie C Y; Adeyemo, Adebowale A; Allison, Matthew A; Bielak, Lawrence F; Chen, Guanjie; Graff, Mariaelisa; Irvin, Marguerite R; Rhie, Suhn K; Li, Guo; Liu, Yongmei; Liu, Youfang; Lu, Yingchang; Nalls, Michael A; Sun, Yan V; Wojczynski, Mary K; Yanek, Lisa R; Aldrich, Melinda C; Ademola, Adeyinka; Amos, Christopher I; Bandera, Elisa V; Bock, Cathryn H; Britton, Angela; Broeckel, Ulrich; Cai, Quiyin; Caporaso, Neil E; Carlson, Chris S; Carpten, John; Casey, Graham; Chen, Wei-Min; Chen, Fang; Chen, Yii-Der I; Chiang, Charleston W K; Coetzee, Gerhard A; Demerath, Ellen; Deming-Halverson, Sandra L; Driver, Ryan W; Dubbert, Patricia; Feitosa, Mary F; Feng, Ye; Freedman, Barry I; Gillanders, Elizabeth M; Gottesman, Omri; Guo, Xiuqing; Haritunians, Talin; Harris, Tamara; Harris, Curtis C; Hennis, Anselm J M; Hernandez, Dena G; McNeill, Lorna H; Howard, Timothy D; Howard, Barbara V; Howard, Virginia J; Johnson, Karen C; Kang, Sun J; Keating, Brendan J; Kolb, Suzanne; Kuller, Lewis H; Kutlar, Abdullah; Langefeld, Carl D; Lettre, Guillaume; Lohman, Kurt; Lotay, Vaneet; Lyon, Helen; Manson, Joann E; Maixner, William; Meng, Yan A; Monroe, Kristine R; Morhason-Bello, Imran; Murphy, Adam B; Mychaleckyj, Josyf C; Nadukuru, Rajiv; Nathanson, Katherine L; Nayak, Uma; N'diaye, Amidou; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M Cristina; Neslund-Dudas, Christine; Neuhouser, Marian; Nyante, Sarah; Ochs-Balcom, Heather; Ogunniyi, Adesola; Ogundiran, Temidayo O; Ojengbede, Oladosu; Olopade, Olufunmilayo I; Palmer, Julie R; Ruiz-Narvaez, Edward A; Palmer, Nicholette D; Press, Michael F; Rampersaud, Evandine; Rasmussen-Torvik, Laura J; Rodriguez-Gil, Jorge L; Salako, Babatunde; Schadt, Eric E; Schwartz, Ann G; Shriner, Daniel A; Siscovick, David; Smith, Shad B; Wassertheil-Smoller, Sylvia; Speliotes, Elizabeth K; Spitz, Margaret R; Sucheston, Lara; Taylor, Herman; Tayo, Bamidele O; Tucker, Margaret A; Van Den Berg, David J; Edwards, Digna R Velez; Wang, Zhaoming; Wiencke, John K; Winkler, Thomas W; Witte, John S; Wrensch, Margaret; Wu, Xifeng; Yang, James J; Levin, Albert M; Young, Taylor R; Zakai, Neil A; Cushman, Mary; Zanetti, Krista A; Zhao, Jing Hua; Zhao, Wei; Zheng, Yonglan; Zhou, Jie; Ziegler, Regina G; Zmuda, Joseph M; Fernandes, Jyotika K; Gilkeson, Gary S; Kamen, Diane L; Hunt, Kelly J; Spruill, Ida J; Ambrosone, Christine B; Ambs, Stefan; Arnett, Donna K; Atwood, Larry; Becker, Diane M; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Borecki, Ingrid B; Bottinger, Erwin P; Bowden, Donald W; Burke, Gregory; Chanock, Stephen J; Cooper, Richard S; Ding, Jingzhong; Duggan, David; Evans, Michele K; Fox, Caroline; Garvey, W Timothy; Bradfield, Jonathan P; Hakonarson, Hakon; Grant, Struan F A; Hsing, Ann; Chu, Lisa; Hu, Jennifer J; Huo, Dezheng; Ingles, Sue A; John, Esther M; Jordan, Joanne M; Kabagambe, Edmond K; Kardia, Sharon L R; Kittles, Rick A; Goodman, Phyllis J; Klein, Eric A; Kolonel, Laurence N; Le Marchand, Loic; Liu, Simin; McKnight, Barbara; Millikan, Robert C; Mosley, Thomas H; Padhukasahasram, Badri; Williams, L Keoki; Patel, Sanjay R; Peters, Ulrike; Pettaway, Curtis A; Peyser, Patricia A; Psaty, Bruce M; Redline, Susan; Rotimi, Charles N; Rybicki, Benjamin A; Sale, Michèle M; Schreiner, Pamela J; Signorello, Lisa B; Singleton, Andrew B; Stanford, Janet L; Strom, Sara S; Thun, Michael J; Vitolins, Mara; Zheng, Wei; Moore, Jason H; Williams, Scott M; Ketkar, Shamika; Zhu, Xiaofeng; Zonderman, Alan B; Kooperberg, Charles; Papanicolaou, George J; Henderson, Brian E; Reiner, Alex P; Hirschhorn, Joel N; Loos, Ruth J F; North, Kari E; Haiman, Christopher A

    2013-06-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

  7. A Meta-Analysis Identifies New Loci Associated with Body Mass index in Individuals of African Ancestry

    PubMed Central

    Monda, Keri L.; Chen, Gary K.; Taylor, Kira C.; Palmer, Cameron; Edwards, Todd L.; Lange, Leslie A.; Ng, Maggie C.Y.; Adeyemo, Adebowale A.; Allison, Matthew A.; Bielak, Lawrence F.; Chen, Guanji; Graff, Mariaelisa; Irvin, Marguerite R.; Rhie, Suhn K.; Li, Guo; Liu, Yongmei; Liu, Youfang; Lu, Yingchang; Nalls, Michael A.; Sun, Yan V.; Wojczynski, Mary K.; Yanek, Lisa R.; Aldrich, Melinda C.; Ademola, Adeyinka; Amos, Christopher I.; Bandera, Elisa V.; Bock, Cathryn H.; Britton, Angela; Broeckel, Ulrich; Cai, Quiyin; Caporaso, Neil E.; Carlson, Chris; Carpten, John; Casey, Graham; Chen, Wei-Min; Chen, Fang; Chen, Yii-Der I.; Chiang, Charleston W.K.; Coetzee, Gerhard A.; Demerath, Ellen; Deming-Halverson, Sandra L.; Driver, Ryan W.; Dubbert, Patricia; Feitosa, Mary F.; Freedman, Barry I.; Gillanders, Elizabeth M.; Gottesman, Omri; Guo, Xiuqing; Haritunians, Talin; Harris, Tamara; Harris, Curtis C.; Hennis, Anselm JM; Hernandez, Dena G.; McNeill, Lorna H.; Howard, Timothy D.; Howard, Barbara V.; Howard, Virginia J.; Johnson, Karen C.; Kang, Sun J.; Keating, Brendan J.; Kolb, Suzanne; Kuller, Lewis H.; Kutlar, Abdullah; Langefeld, Carl D.; Lettre, Guillaume; Lohman, Kurt; Lotay, Vaneet; Lyon, Helen; Manson, JoAnn E.; Maixner, William; Meng, Yan A.; Monroe, Kristine R.; Morhason-Bello, Imran; Murphy, Adam B.; Mychaleckyj, Josyf C.; Nadukuru, Rajiv; Nathanson, Katherine L.; Nayak, Uma; N’Diaye, Amidou; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Neslund-Dudas, Christine; Neuhouser, Marian; Nyante, Sarah; Ochs-Balcom, Heather; Ogunniyi, Adesola; Ogundiran, Temidayo O.; Ojengbede, Oladosu; Olopade, Olufunmilayo I.; Palmer, Julie R.; Ruiz-Narvaez, Edward A.; Palmer, Nicholette D.; Press, Michael F.; Rampersaud, Evandine; Rasmussen-Torvik, Laura J.; Rodriguez-Gil, Jorge L.; Salako, Babatunde; Schadt, Eric E.; Schwartz, Ann G.; Shriner, Daniel A.; Siscovick, David; Smith, Shad B.; Wassertheil-Smoller, Sylvia; Speliotes, Elizabeth K.; Spitz, Margaret R.; Sucheston, Lara; Taylor, Herman; Tayo, Bamidele O.; Tucker, Margaret A.; Van Den Berg, David J.; Velez Edwards, Digna R.; Wang, Zhaoming; Wiencke, John K.; Winkler, Thomas W.; Witte, John S.; Wrensch, Margaret; Wu, Xifeng; Yang, James J.; Levin, Albert M.; Young, Taylor R.; Zakai, Neil A.; Cushman, Mary; Zanetti, Krista A.; Zhao, Jing Hua; Zhao, Wei; Zheng, Yonglan; Zhou, Jie; Ziegler, Regina G.; Zmuda, Joseph M.; Fernandes, Jyotika K.; Gilkeson, Gary S.; Kamen, Diane L.; Hunt, Kelly J.; Spruill, Ida J.; Ambrosone, Christine B.; Ambs, Stefan; Arnett, Donna K.; Atwood, Larry; Becker, Diane M.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Borecki, Ingrid B.; Bottinger, Erwin P.; Bowden, Donald W.; Burke, Gregory; Chanock, Stephen J.; Cooper, Richard S.; Ding, Jingzhong; Duggan, David; Evans, Michele K.; Fox, Caroline; Garvey, W. Timothy; Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F.A.; Hsing, Ann; Chu, Lisa; Hu, Jennifer J.; Huo, Dezheng; Ingles, Sue A.; John, Esther M.; Jordan, Joanne M.; Kabagambe, Edmond K.; Kardia, Sharon L.R.; Kittles, Rick A.; Goodman, Phyllis J.; Klein, Eric A.; Kolonel, Laurence N.; Le Marchand, Loic; Liu, Simin; McKnight, Barbara; Millikan, Robert C.; Mosley, Thomas H.; Padhukasahasram, Badri; Williams, L. Keoki; Patel, Sanjay R.; Peters, Ulrike; Pettaway, Curtis A.; Peyser, Patricia A.; Psaty, Bruce M.; Redline, Susan; Rotimi, Charles N.; Rybicki, Benjamin A.; Sale, Michèle M.; Schreiner, Pamela J.; Signorello, Lisa B.; Singleton, Andrew B.; Stanford, Janet L.; Strom, Sara S.; Thun, Michael J.; Vitolins, Mara; Zheng, Wei; Moore, Jason H.; Williams, Scott M.; Zhu, Xiaofeng; Zonderman, Alan B.; Kooperberg, Charles; Papanicolaou, George; Henderson, Brian E.; Reiner, Alex P.; Hirschhorn, Joel N.; Loos, Ruth JF; North, Kari E.; Haiman, Christopher A.

    2013-01-01

    Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry, and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one novel locus at 5q33 (GALNT10, rs7708584, p=3.4×10−11) and another at 7p15 when combined with data from the Giant consortium (MIR148A/NFE2L3, rs10261878, p=1.2×10−10). We also found suggestive evidence of an association at a third locus at 6q16 in the African ancestry sample (KLHL32, rs974417, p=6.9×10−8). Thirty-two of the 36 previously established BMI variants displayed directionally consistent effect estimates in our GWAS (binomial p=9.7×10−7), of which five reached genome-wide significance. These findings provide strong support for shared BMI loci across populations as well as for the utility of studying ancestrally diverse populations. PMID:23583978

  8. Platelet, monocyte and neutrophil activation and glucose tolerance in South African Mixed Ancestry individuals

    PubMed Central

    Davison, Glenda M.; Nkambule, Bongani B.; Mkandla, Zibusiso; Hon, Gloudina M.; Kengne, Andre P.; Erasmus, Rajiv T.; Matsha, Tandi E.

    2017-01-01

    Platelet activation has been described in patients with chronic inflammation, however in type 2 diabetes mellitus it remains controversial. We compared levels of platelet leucocyte aggregates, monocyte and granulocyte activation across glucose tolerance statuses in mixed ancestry South Africans. Individuals (206) were recruited from Bellville-South, Cape Town, and included 66% with normal glucose tolerance, 18.7% pre-diabetes, 8.7% screen-detected diabetes and 6.3% known diabetes. Monocyte and neutrophil activation were measured by calculating the percentage of cells expressing CD142 and CD69 while platelet monocyte aggregates were defined as CD14++ CD42b+ events and platelet neutrophil aggregates as CD16++ CD42b+ events. The percentage of monocytes and neutrophils expressing CD69 and CD142 was significantly higher in known diabetes and prediabetes, but, lowest in screen-detected diabetes (both p ≤ 0.016). The pattern was similar for platelet monocyte and neutrophil aggregates (both p ≤ 0.003). In robust linear regressions adjusted for age and gender, known diabetes was significantly and positively associated with the percentage of monocytes expressing CD69 [beta 11.06 (p = 0.016)] and CD42b (PMAs) [19.51 (0.003)] as well as the percentage of neutrophils expressing CD69 [14.19 (<0.0001)] and CD42b [17.7 (0.001)]. We conclude that monitoring platelet activation in diagnosed diabetic patients may have a role in the management and risk stratification. PMID:28091589

  9. A DPYD variant (Y186C) in individuals of african ancestry is associated with reduced DPD enzyme activity.

    PubMed

    Offer, S M; Lee, A M; Mattison, L K; Fossum, C; Wegner, N J; Diasio, R B

    2013-07-01

    5-Fluorouracil (5-FU) is used to treat many aggressive cancers, such as those of the colon, breast, and head and neck. The responses to 5-FU, with respect to both toxicity and efficacy, vary among racial groups, potentially because of variability in the activity levels of the enzyme dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene). In this study, the genetic associations between DPYD variations and circulating mononuclear-cell DPD enzyme activity were evaluated in 94 African-American and 81 European-American volunteers. The DPYD-Y186C variant was unique to individuals of African ancestry, and DPD activity was 46% lower in carriers as compared with noncarriers (279 ± 35 vs. 514 ± 168 pmol 5-FU min(-1) mg(-1); P = 0.00029). In this study, 26% of the African Americans with reduced DPD activity were carriers of Y186C. In the African-American cohort, after excluding Y186C carriers, homozygous carriers of C29R showed 27% higher DPD activity as compared with noncarriers (609 ± 152 and 480 ± 152 pmol 5-FU min(-1) mg(-1), respectively; P = 0.013).

  10. Epidermal gene expression and ethnic pigmentation variations among individuals of Asian, European and African ancestry.

    PubMed

    Yin, Lanlan; Coelho, Sergio G; Ebsen, Dominik; Smuda, Christoph; Mahns, Andre; Miller, Sharon A; Beer, Janusz Z; Kolbe, Ludger; Hearing, Vincent J

    2014-10-01

    Differences in visible skin pigmentation give rise to the wide variation of skin colours seen in racial/ethnic populations. Skin pigmentation is important not only from cosmetic and psychological points of view, but more importantly because of its implications for the risk of all types of skin cancers, on photoaging, etc. Despite differences in those parameters in Caucasian and Asian skin types, they are remarkably similar in their production and distribution of melanins, and the mechanism(s) underlying their different characteristics have remained obscure. In this study, we used microarray analysis of skin suction blisters to investigate molecular differences underlying the determination of pigmentation in various skin types, and we used immunohistochemistry to validate the expression patterns of several interesting targets that were identified. Intriguingly, Caucasian and Asian skins had highly similar gene expression patterns that differed significantly from the pattern of African skin. The results of this study suggest the dynamic interactions of different types of cells in human skin that regulate its pigmentation, reveal that the known pigmentation genes have a limited contribution and uncover a new array of genes, including NINL and S100A4, that might be involved in that regulation.

  11. Examining population stratification via individual ancestry estimates versus self-reported race.

    PubMed

    Barnholtz-Sloan, Jill S; Chakraborty, Ranajit; Sellers, Thomas A; Schwartz, Ann G

    2005-06-01

    Population stratification has the potential to affect the results of genetic marker studies. Estimating individual ancestry provides a continuous measure to assess population structure in case-control studies of complex disease, instead of using self-reported racial groups. We estimate individual ancestry using the Federal Bureau of Investigation CODIS Core short tandem repeat set of 13 loci using two different analysis methods in a case-control study of early-onset lung cancer. Individual ancestry proportions were estimated for "European" and "West African" groups using published allele frequencies. The majority of Caucasian, non-Hispanics had >50% European ancestry, whereas the majority of African Americans had <20% European ancestry, regardless of ancestry estimation method, although significant overlap by self-reported race and ancestry also existed. When we further investigated the effect of ancestry and self-reported race on the frequency of a lung cancer risk genotype, we found that the frequency of the GSTM1 null genotype varies by individual European ancestry and case-control status within self-reported race (particularly for African Americans). Genetic risk models showed that adjusting for individual European ancestry provided a better fit to the data compared with the model with no group adjustment or adjustment for self-reported race. This study suggests that significant population substructure differences exist that self-reported race alone does not capture and that individual ancestry may be confounded with disease status and/or a candidate gene risk genotype.

  12. African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

    PubMed Central

    Vergara, Candelaria; Murray, Tanda; Rafaels, Nicholas; Lewis, Rachel; Campbell, Monica; Foster, Cassandra; Gao, Li; Faruque, Mezbah; Oliveira, Ricardo Riccio; Carvalho, Edgar; Araujo, Maria Ilma; Cruz, Alvaro A.; Watson, Harold; Mercado, Dilia; Knight-Madden, Jennifer; Ruczinski, Ingo; Dunston, Georgia; Ford, Jean; Caraballo, Luis; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.

    2014-01-01

    Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels. PMID:23554133

  13. One in Four Individuals of African-American Ancestry Harbors a 5.5kb Deletion at chromosome 11q13.1

    PubMed Central

    Zainabadi, Kayvan; Jain, Anuja V.; Donovan, Frank X.; Elashoff, David; Rao, Nagesh P.; Murty, Vundavalli V.; Chandrasekharappa, Settara C.; Srivatsan, Eri S.

    2014-01-01

    Cloning and sequencing of 5.5kb deletion at chromosome 11q13.1 from the HeLa cells, tumorigenic hybrids and two fibroblast cell lines has revealed homologous recombination between AluSx and AluY resulting in the deletion of intervening sequences. Long-range PCR of the 5.5kb sequence in 494 normal lymphocyte samples showed heterozygous deletion in 28.3% of African- American ancestry samples but only in 4.8% of Caucasian samples (p<0.0001). This observation is strengthened by the copy number variation (CNV) data of the HapMap samples which showed that this deletion occurs in 27% of YRI (Yoruba – West African) population but none in non-African populations. The HapMap analysis further identified strong linkage disequilibrium between 5 single nucleotide polymorphisms and the 5.5kb deletion in the people of African ancestry. Computational analysis of 175kb sequence surrounding the deletion site revealed enhanced flexibility, low thermodynamic stability, high repetitiveness, and stable stem-loop/hairpin secondary structures that are hallmarks of common fragile sites. PMID:24412158

  14. African Genetic Ancestry is Associated with Sleep Depth in Older African Americans

    PubMed Central

    Halder, Indrani; Matthews, Karen A.; Buysse, Daniel J.; Strollo, Patrick J.; Causer, Victoria; Reis, Steven E.; Hall, Martica H.

    2015-01-01

    Study Objectives: The mechanisms that underlie differences in sleep characteristics between European Americans (EA) and African Americans (AA) are not fully known. Although social and psychological processes that differ by race are possible mediators, the substantial heritability of sleep characteristics also suggests genetic underpinnings of race differences. We hypothesized that racial differences in sleep phenotypes would show an association with objectively measured individual genetic ancestry in AAs. Design: Cross sectional. Setting: Community-based study. Participants: Seventy AA adults (mean age 59.5 ± 6.7 y; 62% female) and 101 EAs (mean age 60.5 ± 7 y, 39% female). Measurements and Results: Multivariate tests were used to compare the Pittsburgh Sleep Quality Index (PSQI) and in-home polysomnographic measures of sleep duration, sleep efficiency, apnea-hypopnea index (AHI), and indices of sleep depth including percent visually scored slow wave sleep (SWS) and delta EEG power of EAs and AAs. Sleep duration, efficiency, and sleep depth differed significantly by race. Individual % African ancestry (%AF) was measured in AA subjects using a panel of 1698 ancestry informative genetic markers and ranged from 10% to 88% (mean 67%). Hierarchical linear regression showed that higher %AF was associated with lower percent SWS in AAs (β (standard error) = −4.6 (1.5); P = 0.002), and explained 11% of the variation in SWS after covariate adjustment. A similar association was observed for delta power. No association was observed for sleep duration and efficiency. Conclusion: African genetic ancestry is associated with indices of sleep depth in African Americans. Such an association suggests that part of the racial differences in slow-wave sleep may have genetic underpinnings. Citation: Halder I, Matthews KA, Buysse DJ, Strollo PJ, Causer V, Reis SE, Hall MH. African genetic ancestry is associated with sleep depth in older African Americans. SLEEP 2015;38(8):1185–1193

  15. African ancestry protects against Alzheimer's disease-related neuropathology.

    PubMed

    Schlesinger, D; Grinberg, L T; Alba, J G; Naslavsky, M S; Licinio, L; Farfel, J M; Suemoto, C K; de Lucena Ferretti, R E; Leite, R E P; de Andrade, M P; dos Santos, A C F; Brentani, H; Pasqualucci, C A; Nitrini, R; Jacob-Filho, W; Zatz, M

    2013-01-01

    Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of São Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry-informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55-0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21-0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil.

  16. European Ancestry as a Risk Factor for Atrial Fibrillation in African Americans

    PubMed Central

    Marcus, Gregory M.; Alonso, Alvaro; Peralta, Carmen A.; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A.; Fox, Ervin R.; Levitzky, Yamini S.; Mehra, Reena; Kerr, Kathleen F.; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T.; Paltoo, Dina N.; Soliman, Elsayed Z.; Benjamin, Emelia J.; Heckbert, Susan R.

    2010-01-01

    Background Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown if the higher riskis due to genetic or environmental factors. As African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. Methods and Results We studied whites (n=4,543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10,902) and Africa Americans (n=3,517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3,517). Percent European ancestry in African Americans was estimated using 1,747 ancestry informative markers (AIMs) from the Illumina custom ITMAT-Broad-CARe (IBC) array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3,517 ARIC participants developed incident AF. A meta-analysis from the two studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (HR 1.13, 95% CI 1.03–1.23, p=0.007). After adjusting for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% CI 1.07–1.29, p=0.001). A second analysis using 3,192 AIMs from a genome wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. Conclusion European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative. PMID:21098467

  17. Genetic African Ancestry and Markers of Mineral Metabolism in CKD

    PubMed Central

    Parsa, Afshin; Isakova, Tamara; Scialla, Julia J.; Chen, Jing; Flack, John M.; Nessel, Lisa C.; Gupta, Jayanta; Bellovich, Keith A.; Steigerwalt, Susan; Sondheimer, James H.; Wright, Jackson T.; Feldman, Harold I.; Kusek, John W.; Lash, James P.; Wolf, Myles

    2016-01-01

    Background and objectives Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. Design, setting, participants, & measurements In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Results Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). Conclusions A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional

  18. The role of ancestry in TB susceptibility of an admixed South African population.

    PubMed

    Daya, Michelle; van der Merwe, Lize; van Helden, Paul D; Möller, Marlo; Hoal, Eileen G

    2014-07-01

    Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC.

  19. Global and Local Ancestry in African Americans: Implications for Alzheimer’s Disease Risk

    PubMed Central

    Hohman, Timothy J.; Cooke-Bailey, Jessica N.; Reitz, Christiane; Jun, Gyungah; Naj, Adam; Beecham, Gary W.; Liu, Zhi; Carney, Regina M.; Vance, Jeffrey M.; Cuccaro, Michael L.; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark W.; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hardy, John; Hendrie, Hugh C.; Hall, Kathleen S.; Goate, Alison M.; Lang, Rosalyn; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Farrer, Lindsay A.; Martin, Eden R.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Mayeux, Richard; Haines, Jonathan L.; Thornton-Wells, Tricia A.

    2015-01-01

    African American (AA) individuals have a higher risk for late-onset Alzheimer’s disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the AD-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered. We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences. Exploratory post-hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses. PMID:26092349

  20. Genomic ancestry of North Africans supports back-to-Africa migrations.

    PubMed

    Henn, Brenna M; Botigué, Laura R; Gravel, Simon; Wang, Wei; Brisbin, Abra; Byrnes, Jake K; Fadhlaoui-Zid, Karima; Zalloua, Pierre A; Moreno-Estrada, Andres; Bertranpetit, Jaume; Bustamante, Carlos D; Comas, David

    2012-01-01

    North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from "back-to-Africa" gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa.

  1. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

    PubMed

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-09-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

  2. Genetics of stroke in a UK African ancestry case-control study

    PubMed Central

    Rutten-Jacobs, Loes; Curtis, Charles; Patel, Hamel; Breen, Gerome; Newhouse, Stephen; Lewis, Cathryn M.; Markus, Hugh S.

    2017-01-01

    Objective: Despite epidemiologic data showing an increased stroke incidence in African ancestry populations, genetic studies in this group have so far been limited, and there has been little characterization of the genetic contribution to stroke liability in this population, particularly for stroke subtypes. Methods: We evaluated the evidence that genetic factors contribute to stroke and stroke subtypes in a population of 917 African and African Caribbean stroke cases and 868 matched controls from London, United Kingdom. We (1) estimated the heritability of stroke in this population using genomic-relatedness matrix-restricted maximum likelihood approaches, (2) assessed loci associated with stroke in Europeans in our population, and (3) evaluated the influence of genetic factors underlying cardiovascular risk factors on stroke using polygenic risk scoring. Results: Our results indicate a substantial genetic contribution to stroke risk in African ancestry populations (h2 = 0.35 [SE = 0.19], p = 0.043). Polygenic risk scores indicate that cardiovascular risk scores contribute to the genetic liability (odds ratio [OR] 1.09 [95% confidence interval (CI) 1.01–1.17], p = 0.029) and point to a strong influence of type 2 diabetes in large vessel stroke (OR 1.62 [95% CI 1.19–2.22], p = 0.0024). Single nucleotide polymorphisms associated with ischemic stroke in Europeans shared direction of effect in SLESS (p = 0.031), suggesting that disease mechanisms are shared across ancestries. Conclusions: Stroke in African ancestry populations is highly heritable and influenced by genetic determinants underlying cardiovascular risk factors. In addition, stroke loci identified in Europeans share direction of effect in African populations. Future genome-wide association studies must focus on incorporating African ancestry individuals. PMID:28349126

  3. Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

    PubMed Central

    Kessler, Michael D.; Yerges-Armstrong, Laura; Taub, Margaret A.; Shetty, Amol C.; Maloney, Kristin; Jeng, Linda Jo Bone; Ruczinski, Ingo; Levin, Albert M.; Williams, L. Keoki; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Boorgula, Meher Preethi; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Scott, Alan F.; Vergara, Candelaria; Gao, Jingjing; Hu, Yijuan; Johnston, Henry Richard; Qin, Zhaohui S.; Padhukasahasram, Badri; Dunston, Georgia M.; Faruque, Mezbah U.; Kenny, Eimear E.; Gietzen, Kimberly; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-YounA; Kumar, Rajesh; Schleimer, Robert; Bustamante, Carlos; De La Vega, Francisco M.; Gignoux, Chris R.; Shringarpure, Suyash S.; Musharoff, Shaila; Wojcik, Genevieve; Burchard, Esteban G.; Eng, Celeste; Gourraud, Pierre-Antoine; Hernandez, Ryan D.; Lizee, Antoine; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O.; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Abecasis, Goncalo; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Pissamai, Maul R. N.; Trevor, Maul R. N.; Watson, Harold; Araujo, Maria Ilma; Oliveira, Ricardo Riccio; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Herrera-Paz, Edwin Francisco; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Vasquez, Olga Marina; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria; O'Connor, Timothy D.

    2016-01-01

    To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=−0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations. PMID:27725664

  4. Glucose Tolerance, MTHFR C677T and NOS3 G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

    PubMed Central

    Mutize, Tinashe; Erasmus, Rajiv T.

    2016-01-01

    The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p ≤ 0.033) and in screen-detected diabetes compared to known diabetes on treatment (p = 0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p > 0.999). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β = 0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control. PMID:27990443

  5. Disparities in breast cancer and african ancestry: a global perspective.

    PubMed

    Newman, Lisa A

    2015-01-01

    Recognition of breast cancer disparities between African-American and White American women has generated exciting research opportunities investigating the biologic and hereditary factors that contribute to the observed outcome differences, leading to international studies of breast cancer in Africa. The study of breast cancer in women with African ancestry has opened the door to unique investigations regarding breast cancer subtypes and the genetics of this disease. International research efforts can advance our understanding of race/ethnicity-associated breast cancer disparities within the USA; the pathogenesis of triple negative breast cancer; and hereditary susceptibility for breast cancer.

  6. African genetic ancestry is associated with a protective effect on Dengue severity in colombian populations.

    PubMed

    Chacón-Duque, Juan Camilo; Adhikari, Kaustubh; Avendaño, Efren; Campo, Omer; Ramirez, Ruth; Rojas, Winston; Ruiz-Linares, Andrés; Restrepo, Berta Nelly; Bedoya, Gabriel

    2014-10-01

    The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African ancestry, 95% confidence interval (0.934-0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947-0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952-0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for

  7. Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry

    PubMed Central

    Tanaka, Toshiko; Towers, G. Wayne; Verhoef, Hans; Veenemans, Jacobien; Talsma, Elise F.; Harryvan, Jan; Boekschoten, Mark V.; Feskens, Edith J.; Melse-Boonstra, Alida

    2016-01-01

    Background Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. Methods We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. Results In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. Conclusions In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations. PMID:27332551

  8. The Genetic Contribution of West-African Ancestry to Protection against Central Obesity in African-American Men but Not Women: Results from the ARIC and MESA Studies

    PubMed Central

    Klimentidis, Yann C.; Arora, Amit; Zhou, Jin; Kittles, Rick; Allison, David B.

    2016-01-01

    Over 80% of African-American (AA) women are overweight or obese. A large racial disparity between AA and European-Americans (EA) in obesity rates exists among women, but curiously not among men. Although socio-economic and/or cultural factors may partly account for this race-by-sex interaction, the potential involvement of genetic factors has not yet been investigated. Among 2814 self-identified AA in the Atherosclerosis Risk in Communities study, we estimated each individual's degree of West-African genetic ancestry using 3437 ancestry informative markers. We then tested whether sex modifies the association between West-African genetic ancestry and body mass index (BMI), waist-circumference (WC), and waist-to-hip ratio (WHR), adjusting for income and education levels, and examined associations of ancestry with the phenotypes separately in males and females. We replicated our findings in the Multi-Ethnic Study of Atherosclerosis (n = 1611 AA). In both studies, we find that West-African ancestry is negatively associated with obesity, especially central obesity, among AA men, but not among AA women (pinteraction = 4.14 × 10−5 in pooled analysis of WHR). In conclusion, our results suggest that the combination of male gender and West-African genetic ancestry is associated with protection against central adiposity, and suggest that the large racial disparity that exists among women, but not men, may be at least partly attributed to genetic factors. PMID:27313598

  9. Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging

    PubMed Central

    2016-01-01

    Background The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. Methodology/Principal Findings We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged ≥ 60 years) of the Bambui (Brazil) population-based cohort study of aging. Potential confounding variables included sociodemographic characteristics and an array of health measures. The prevalence of T. cruzi infection was 37.5% and 56.3% of those infected had a major ECG abnormality. Baseline T. cruzi infection was correlated with higher levels of African and Native American ancestry, which in turn were strongly associated with poor socioeconomic circumstances. Cardiomyopathy in infected persons was not significantly associated with African or Native American ancestry levels. Infected persons with a major ECG abnormality were at increased risk of 15-year mortality relative to their counterparts with no such abnormalities (adjusted hazard ratio = 1.80; 95% 1.41, 2.32). African and Native American ancestry levels had no significant effect modifying this association. Conclusions/Significance Our findings indicate that African and Native American ancestry have no influence on the presence of major ECG abnormalities and had no influence on the ability of an ECG abnormality to predict mortality in older people infected with T. cruzi. In contrast, our results revealed a strong and independent association between prevalent T. cruzi infection and higher levels of African and Native American ancestry. Whether this association is a consequence of genetic background or differential exposure to infection remains to be determined. PMID:27182885

  10. APOL1 and nephropathy progression in populations of African ancestry.

    PubMed

    Freedman, Barry I

    2013-09-01

    Marked familial aggregation of chronic kidney disease suggests that inherited factors play a major role in nephropathy susceptibility. Molecular genetics analyses have identified a number of genes reproducibly associated with a broad range of renal phenotypes. Most associations show polygenic inheritance patterns with limited effect size. In contrast, genetic association between the apolipoprotein L1 (APOL1) gene and several severe nondiabetic forms of kidney disease in African Americans approach Mendelian inheritance patterns and account for a large proportion of glomerulosclerosis in populations of African ancestry. Emerging data support an important role for APOL1 in the progression of diverse etiologies of kidney disease, in concert with requisite environmental (gene*environment) and inherited (gene*gene) interactions. This article reviews the current status of APOL1-associated nephropathy and discusses research questions under active investigation in the search for a cure for these severe and often progressive kidney diseases.

  11. Lactase persistence alleles reveal partial East African ancestry of southern African Khoe pastoralists.

    PubMed

    Breton, Gwenna; Schlebusch, Carina M; Lombard, Marlize; Sjödin, Per; Soodyall, Himla; Jakobsson, Mattias

    2014-04-14

    The ability to digest milk into adulthood, lactase persistence (LP), as well as specific genetic variants associated with LP, is heterogeneously distributed in global populations. These variants were most likely targets of selection when some populations converted from hunter-gatherer to pastoralist or farming lifestyles. Specific LP polymorphisms are associated with particular geographic regions and populations; however, they have not been extensively studied in southern Africa. We investigate the LP-regulatory region in 267 individuals from 13 southern African populations (including descendants of hunter-gatherers, pastoralists, and agropastoralists), providing the first comprehensive study of the LP-regulatory region in a large group of southern Africans. The "East African" LP single-nucleotide polymorphism (SNP) (14010G>C) was found at high frequency (>20%) in a strict pastoralist Khoe population, the Nama of Namibia, suggesting a connection to East Africa, whereas the "European" LP SNP (13910C>T) was found in populations of mixed ancestry. Using genome-wide data from various African populations, we identify admixture (13%) in the Nama, from an Afro-Asiatic group dating to >1,300 years ago, with the remaining fraction of their genomes being from San hunter-gatherers. We also find evidence of selection around the LCT gene among Khoe-speaking groups, and the substantial frequency of the 14010C variant among the Nama is best explained by adaptation to digesting milk. These genome-local and genome-wide results support a model in which an East African group brought pastoralist practices to southern Africa and admixed with local hunter-gatherers to form the ancestors of Khoe people.

  12. The Genomic Ancestry of Individuals from Different Geographical Regions of Brazil Is More Uniform Than Expected

    PubMed Central

    Pena, Sérgio D. J.; Di Pietro, Giuliano; Fuchshuber-Moraes, Mateus; Genro, Julia Pasqualini; Hutz, Mara H.; Kehdy, Fernanda de Souza Gomes; Kohlrausch, Fabiana; Magno, Luiz Alexandre Viana; Montenegro, Raquel Carvalho; Moraes, Manoel Odorico; de Moraes, Maria Elisabete Amaral; de Moraes, Milene Raiol; Ojopi, Élida B.; Perini, Jamila A.; Racciopi, Clarice; Ribeiro-dos-Santos, Ândrea Kely Campos; Rios-Santos, Fabrício; Romano-Silva, Marco A.; Sortica, Vinicius A.; Suarez-Kurtz, Guilherme

    2011-01-01

    Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a “total ancestry” estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries - a phenomenon described and intended as the “whitening of Brazil” - is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be

  13. African Ancestry Gradient Is Associated with Lower Systemic F2-Isoprostane Levels

    PubMed Central

    Annor, Francis; Okosun, Ike; Gower, Barbara A.

    2017-01-01

    Context. Low levels of systemic F2-isoprostanes (F2-IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F2-IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective. To examine differences in plasma F2-IsoPs in three groups with a priori different proportion of African ancestry: non-Hispanic Whites (NHWs), US-born African Americans (AAs), and West African immigrants (WAI). Design. Cross-sectional study. Setting. Georgia residents recruited from church communities. Participants. 218 males and females 25–74 years of age, who are self-identified as NHW (n = 83), AA (n = 56), or WAI (n = 79). Main Outcome Measure(s). Plasma F2-IsoPs quantified by gas chromatography-mass spectrometry. Results. After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F2-IsoP than AA (beta-coefficient = −9.8, p < 0.001) and AA had lower levels than NHW (beta-coefficient = −30.3, p < 0.001). Similarly, among healthy nonobese participants, F2-IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion. Plasma F2-IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F2-IsoP levels can serve as means to improve race-specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment. PMID:28250893

  14. Age at breast cancer diagnosis in populations of african and European ancestry.

    PubMed

    Kadhel, Philippe; Multigner, Luc

    2014-01-01

    Based on US national cancer registry data, age differences at breast cancer diagnosis have been reported between African-American women and European-American women. Such differences between populations of African and European ancestry have not been studied in other countries at a nationwide level. Here, we report and compare descriptive nationwide epidemiological indicators of invasive breast cancer for the populations of European ancestry living in the US and in mainland France and for women of African ancestry living in the US and in the French West Indies (Martinique and Guadeloupe). Based on the available data, we determined age frequency distributions, world age-standardized incidence, and the distribution of expected cases of breast cancer in a standard population of women by age. The age frequency distributions revealed that women of African ancestry were younger at diagnosis than women of European ancestry. By contrast, compared with the US regardless of ancestry and mainland France, the standardized incidences appeared lower, and the largest numbers of expected cases younger, in the French West Indies. The populations with African ancestry were not homogeneous in terms of epidemiologic indicators of age-related breast cancer. These descriptive findings suggest that populations of African ancestry cannot be considered uniform when determining whether it would be appropriate to decrease the age of entry into screening programs for breast cancer.

  15. Differentiation of African Components of Ancestry to Stratify Groups in a Case–Control Study of a Brazilian Urban Population

    PubMed Central

    Hirata, Mario H.; Luchessi, Andre D.; Genvigir, Fabiana D.V.; Cerda, Alvaro; Rodrigues, Alice C.; Willrich, Maria A.V.; Arazi, Simone S.; Dorea, Egidio L.; Bernik, Marcia M.S.; Faludi, Andre A.; Bertolami, Marcelo C.; Santos, Carla; Carracedo, Ángel; Salas, Antonio; Freire, Ana; Lareu, Maria Victoria; Phillips, Christopher; Porras-Hurtado, Liliana; Fondevila, Manuel; Hirata, Rosario D.C.

    2012-01-01

    Background: Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. Methods: We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case–control association study of a Brazilian urban sample. Results: One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA <0.25 and >0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. Conclusions: The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers. PMID:22288895

  16. A single-tube 27-plex SNP assay for estimating individual ancestry and admixture from three continents.

    PubMed

    Wei, Yi-Liang; Wei, Li; Zhao, Lei; Sun, Qi-Fan; Jiang, Li; Zhang, Tao; Liu, Hai-Bo; Chen, Jian-Gang; Ye, Jian; Hu, Lan; Li, Cai-Xia

    2016-01-01

    A single-tube multiplex assay of a small set of ancestry-informative markers (AIMs) for effectively estimating individual ancestry and admixture is an ideal forensic tool to trace the population origin of an unknown DNA sample. We present a newly developed 27-plex single nucleotide polymorphism (SNP) panel with highly robust and balanced differential power to perfectly assign individuals to African, European, and East Asian ancestries. Evaluating 968 previously described intercontinental AIMs from three HapMap population genotyping datasets (Yoruban in Ibadan, Nigeria (YRI); Utah residents with Northern and Western European ancestry from the Centre de'Etude du Polymorphism Humain (CEPH) collection (CEU); and Han Chinese in Beijing, China (CHB)), the best set of markers was selected on the basis of Hardy-Weinberg equilibrium (p > 0.00001), population-specific allele frequency (two of three δ values >0.5), according to linkage disequilibrium (r (2) < 0.2), and capable of being multiplexed in one tube and detected by capillary electrophoresis. The 27-SNP panel was first validated by assigning the ancestry of the 11 populations in the HapMap project. Then, we tested the 27-plex SNP assay with 1164 individuals from 17 additional populations. The results demonstrated that the SNP panel was successful for ancestry inference of individuals with African, European, and East Asian ancestry. Furthermore, the system performed well when inferring the admixture of Eurasians (EUR/EAS) after analyzing admixed populations from Xinjiang (Central Asian) as follows: Tajik (68:27), Uyghur (49:46), Kirgiz (40:57), and Kazak (36:60). For individual analyses, we interpreted each sample with a three-ancestry component percentage and a population match probability sequence. This multiplex assay is a convenient and cost-effective tool to assist in criminal investigations, as well as to correct for the effects of population stratification for case-control studies.

  17. Race, genetic West African ancestry, and prostate cancer prediction by prostate-specific antigen in prospectively screened high-risk men.

    PubMed

    Giri, Veda N; Egleston, Brian; Ruth, Karen; Uzzo, Robert G; Chen, David Y T; Buyyounouski, Mark; Raysor, Susan; Hooker, Stanley; Torres, Jada Benn; Ramike, Teniel; Mastalski, Kathleen; Kim, Taylor Y; Kittles, Rick

    2009-03-01

    "Race-specific" prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with > or =1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 to 4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. "Race-specific" PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.

  18. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

    PubMed Central

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-01-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  19. Breast cancer disparities: high-risk breast cancer and African ancestry.

    PubMed

    Newman, Lisa A

    2014-07-01

    African American women have a lower lifetime incidence of breast cancer than white/Caucasian Americans yet have a higher risk of breast cancer mortality. African American women are also more likely to be diagnosed with breast cancer at young ages, and they have higher risk for the biologically more aggressive triple-negative breast cancers. These features are also more common among women from western, sub-Saharan Africa who share ancestry with African Americans, and this prompts questions regarding an association between African ancestry and inherited susceptibility for certain patterns of mammary carcinogenesis.

  20. A SNP test to identify Africanized honeybees via proportion of 'African' ancestry.

    PubMed

    Chapman, Nadine C; Harpur, Brock A; Lim, Julianne; Rinderer, Thomas E; Allsopp, Michael H; Zayed, Amro; Oldroyd, Benjamin P

    2015-11-01

    The honeybee, Apis mellifera, is the world's most important pollinator and is ubiquitous in most agricultural ecosystems. Four major evolutionary lineages and at least 24 subspecies are recognized. Commercial populations are mainly derived from subspecies originating in Europe (75-95%). The Africanized honeybee is a New World hybrid of A. m. scutellata from Africa and European subspecies, with the African component making up 50-90% of the genome. Africanized honeybees are considered undesirable for bee-keeping in most countries, due to their extreme defensiveness and poor honey production. The international trade in honeybees is restricted, due in part to bans on the importation of queens (and semen) from countries where Africanized honeybees are extant. Some desirable strains from the United States of America that have been bred for traits such as resistance to the mite Varroa destructor are unfortunately excluded from export to countries such as Australia due to the presence of Africanized honeybees in the USA. This study shows that a panel of 95 single nucleotide polymorphisms, chosen to differentiate between the African, Eastern European and Western European lineages, can detect Africanized honeybees with a high degree of confidence via ancestry assignment. Our panel therefore offers a valuable tool to mitigate the risks of spreading Africanized honeybees across the globe and may enable the resumption of queen and bee semen imports from the Americas.

  1. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype.

    PubMed

    Krause, Amanda; Mitchell, Claire; Essop, Fahmida; Tager, Susan; Temlett, James; Stevanin, Giovanni; Ross, Christopher; Rudnicki, Dobrila; Margolis, Russell

    2015-10-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations.

  2. JUNCTOPHILIN 3 (JPH3) EXPANSION MUTATIONS CAUSING HUNTINGTON DISEASE LIKE 2 (HDL2) ARE COMMON IN SOUTH AFRICAN PATIENTS WITH AFRICAN ANCESTRY AND A HUNTINGTON DISEASE PHENOTYPE

    PubMed Central

    Krause, A; Mitchell, CL; Essop, F; Tager, S; Temlett, J; Stevanin, G; Ross, CA; Rudnicki, DD; Margolis, RL

    2015-01-01

    Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. PMID:26079385

  3. Amerindian (but not African or European) ancestry is significantly associated with diurnal preference within an admixed Brazilian population.

    PubMed

    Egan, Kieren J; Campos Santos, Hadassa; Beijamini, Felipe; Duarte, Núbia E; Horimoto, Andréa R V R; Taporoski, Tâmara P; Vallada, Homero; Negrão, André B; Krieger, José E; Pedrazzoli, Mário; Knutson, Kristen L; Pereira, Alexandre C; von Schantz, Malcolm

    2017-01-01

    Significant questions remain unanswered regarding the genetic versus environmental contributions to racial/ethnic differences in sleep and circadian rhythms. We addressed this question by investigating the association between diurnal preference, using the morningness-eveningness questionnaire (MEQ), and genetic ancestry within the Baependi Heart Study cohort, a highly admixed Brazilian population based in a rural town. Analysis was performed using measures of ancestry, using the Admixture program, and MEQ from 1,453 individuals. We found an association between the degree of Amerindian (but not European of African) ancestry and morningness, equating to 0.16 units for each additional percent of Amerindian ancestry, after adjustment for age, sex, education, and residential zone. To our knowledge, this is the first published report identifying an association between genetic ancestry and MEQ, and above all, the first one based on ancestral contributions within individuals living in the same community. This previously unknown ancestral dimension of diurnal preference suggests a stratification between racial/ethnic groups in an as yet unknown number of genetic polymorphisms.

  4. The Genetic Ancestry of African Americans, Latinos, and European Americans across the United States

    PubMed Central

    Bryc, Katarzyna; Durand, Eric Y.; Macpherson, J. Michael; Reich, David; Mountain, Joanna L.

    2015-01-01

    Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry. PMID:25529636

  5. The genetic ancestry of African Americans, Latinos, and European Americans across the United States.

    PubMed

    Bryc, Katarzyna; Durand, Eric Y; Macpherson, J Michael; Reich, David; Mountain, Joanna L

    2015-01-08

    Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry.

  6. Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry.

    PubMed

    Huo, Dezheng; Zheng, Yonglan; Ogundiran, Temidayo O; Adebamowo, Clement; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Simon, Michael S; John, Esther M; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M Cristina; Ambs, Stefan; Niu, Qun; Zhang, Jing; Cox, Nancy J; Olopade, Olufunmilayo I

    2012-04-01

    Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case-control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04-1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10-1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00-1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer.

  7. Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry

    PubMed Central

    Huo, Dezheng; Zheng, Yonglan; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Simon, Michael S.; John, Esther M.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M.Cristina; Ambs, Stefan; Niu, Qun; Zhang, Jing; Cox, Nancy J.; Olopade, Olufunmilayo I.

    2012-01-01

    Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case–control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04–1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10–1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00–1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer. PMID:22357627

  8. Higher endothelin concentrations in the fetoplacental unit of pregnant women of African ancestry.

    PubMed

    Carbonne, B; Mignot, T M; Papiernik, E; Ferré, F

    1998-03-01

    Immunoreactive endothelin was assayed in maternal and fetal biologic fluids of women of African and European ancestry with normal singleton pregnancies undergoing cesarean section at term for obstetric reasons. Endothelin concentration was found to be higher in the umbilical vein and artery blood of women of African origin. Higher production of endothelins in the fetoplacental unit may place these women at a greater risk of preeclampsia.

  9. Teaching through the Prism of Difference: A Dialogue among Four Bilingual, African-Ancestry Teachers.

    ERIC Educational Resources Information Center

    Casimir, Myriam; Mattox, Norman; Hays, John; Vasquez, Carla Llewelyn

    2000-01-01

    Four bilingual educators of African ancestry discuss issues that affect them as teachers and that affect their students as ethnolinguistic minorities. The paper discusses views of culture and language; teachers' identity construction; students' identity construction; and a twofold educational response to students' academic and social needs as…

  10. African ancestry is associated with risk of asthma and high total serum IgE in a population from the Caribbean Coast of Colombia.

    PubMed

    Vergara, Candelaria; Caraballo, Luis; Mercado, Dilia; Jimenez, Silvia; Rojas, Winston; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Tsai, Yuhjung J; Gao, Li; Duque, Constanza; Lopez, Sergio; Bedoya, Gabriel; Ruiz-Linares, Andrés; Barnes, Kathleen C

    2009-06-01

    African descended populations exhibit an increased prevalence of asthma and allergies compared to Europeans. One approach to distinguish between environmental and genetic explanations for this difference is to study relationships of asthma risk to individual admixture. We aimed to determine the admixture proportions of a case-control sample from the Caribbean Coast of Colombia currently participating in genetic studies for asthma, and to test for population stratification and association between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 368 asthmatics and 365 non-asthmatics for 52 autosomal ancestry informative markers, six mtDNA haplogroups and nine haplogroups and five microsatellites in Y chromosome. Autosomal admixture proportions, population stratification, and associations between ancestry and the phenotypes were estimated by ADMIXMAP. The average admixture proportions among asthmatics were 42.8% European, 39.9% African and 17.2% Native American and among non-asthmatics they were 44.2% (P = 0.068), 37.6% (P = 0.007) and 18.1% (P = 0.050), respectively. In the total sample, the paternal contributions were 71% European, 25% African and 4.0% Native American and the maternal lineages were 56.8% Native American, and 20.2% African; 22.9% of the individuals carried other non-Native American mtDNA haplogroups. African ancestry was significantly associated with asthma (OR: 2.97; 95% CI: 1.08-8.08), high tIgE (OR: 1.9; 95% CI: 1.17-3.12) and socioeconomic status (OR = 0.64; 95% CI: 0.47-0.87). Significant population stratification was observed in this sample. Our findings indicate that genetic factors can explain the association between asthma and African ancestry and suggest that this sample is a useful resource for performing admixture mapping for asthma.

  11. Extensive Copy Number Variations in Admixed Indian Population of African Ancestry: Potential Involvement in Adaptation

    PubMed Central

    Dash, Debasis; Mukerji, Mitali

    2014-01-01

    Admixture mapping has been enormously resourceful in identifying genetic variations linked to phenotypes, adaptation, and diseases. In this study through analysis of copy number variable regions (CNVRs), we report extensive restructuring in the genomes of the recently admixed African-Indian population (OG-W-IP) that inhabits a highly saline environment in Western India. The study included subjects from OG-W-IP (OG), five different Indian and three HapMap populations that were genotyped using Affymetrix version 6.0 arrays. Copy number variations (CNVs) detected using Birdsuite were used to define CNVRs. Population structure with respect to CNVRs was delineated using random forest approach. OG genomes have a surprising excess of CNVs in comparison to other studied populations. Individual ancestry proportions computed using STRUCTURE also reveals a unique genetic component in OGs. Population structure analysis with CNV genotypes indicates OG to be distant from both the African and Indian ancestral populations. Interestingly, it shows genetic proximity with respect to CNVs to only one Indian population IE-W-LP4, which also happens to reside in the same geographical region. We also observe a significant enrichment of molecular processes related to ion binding and receptor activity in genes encompassing OG-specific CNVRs. Our results suggest that retention of CNVRs from ancestral natives and de novo acquisition of CNVRs could accelerate the process of adaptation especially in an extreme environment. Additionally, this population would be enormously useful for dissecting genes and delineating the involvement of CNVs in salt adaptation. PMID:25398783

  12. Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry

    PubMed Central

    Brewster, Abenaa M; Chavez-MacGregor, Mariana; Brown, Powel

    2015-01-01

    Breast cancer incidence is increasing worldwide, and breast cancer-related mortality is highest in women of African ancestry, who are more likely to have basal-like or triple-negative breast cancer (TNBC) than are women of European ancestry. Identification of cultural, epidemiological, and genetic risk factors that predispose women of African ancestry to TNBC is an active area of research. Despite the aggressive behaviour of TNBC, achievement of a pathological complete response with chemotherapy is associated with good long-term survival outcomes, and sensitivity to chemotherapy does not seem to differ according to ethnic origin. Discovery of the molecular signalling molecules that define TNBC heterogeneity has led to the development of targeted agents such as inhibitors of poly (ADP-ribose) polymerase-1 and mTOR and immunomodulatory drugs that are in the early stages of clinical testing. First, we summarise the existing published work on the differences reported on the epidemiology, biology, and response to systemic treatment of TNBC between women of African ancestry and white women, and identify some gaps in knowledge. Second, we review the opportunities for development of new therapeutic agents in view of the potential high clinical relevance for patients with TNBC irrespective of race or ethnic origin. PMID:25456381

  13. Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome

    PubMed Central

    Tekola-Ayele, Fasil; Doumatey, Ayo P.; Shriner, Daniel; Bentley, Amy R.; Chen, Guanjie; Zhou, Jie; Fasanmade, Olufemi; Johnson, Thomas; Oli, Johnnie; Okafor, Godfrey; Eghan, Benjami A.; Agyenim-Boateng, Kofi; Adebamowo, Clement; Amoah, Albert; Acheampong, Joseph; Adeyemo, Adebowale; Rotimi, Charles N.

    2015-01-01

    The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1,427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86x10−8, OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63x10−8, OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37x10−9, OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52x10−8, Pmeta=7.82x10−9, OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits. PMID:26507551

  14. Genome-wide association study identifies African-ancestry specific variants for metabolic syndrome.

    PubMed

    Tekola-Ayele, Fasil; Doumatey, Ayo P; Shriner, Daniel; Bentley, Amy R; Chen, Guanjie; Zhou, Jie; Fasanmade, Olufemi; Johnson, Thomas; Oli, Johnnie; Okafor, Godfrey; Eghan, Benjami A; Agyenim-Boateng, Kofi; Adebamowo, Clement; Amoah, Albert; Acheampong, Joseph; Adeyemo, Adebowale; Rotimi, Charles N

    2015-12-01

    The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86 × 10(-8), OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63 × 10(-8), OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37 × 10(-9), OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52 × 10(-8), Pmeta=7.82 × 10(-9), OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.

  15. A genome-wide association study of breast cancer in women of African ancestry

    PubMed Central

    Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R.; Hu, Jennifer J.; Rebbeck, Tim R.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Ruiz-Narvaez, Edward A.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; DeMichele, Angela; Chanock, Stephen J.; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong; Huo, Dezheng; Zheng, Yonglan; Cox, Nancy J.; Olopade, Olufunmilayo I.; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Simon, Michael S.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Ambs, Stefan; Hutter, Carolyn M.; Young, Alicia; Kooperberg, Charles; Peters, Ulrike; Rhie, Suhn K.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Christopher A.

    2013-01-01

    Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10−6 and 10−5 in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3×10−6; rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5×10−5). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample. PMID:22923054

  16. A genome-wide association study of breast cancer in women of African ancestry.

    PubMed

    Chen, Fang; Chen, Gary K; Stram, Daniel O; Millikan, Robert C; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R; Hu, Jennifer J; Rebbeck, Tim R; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Ruiz-Narvaez, Edward A; Deming, Sandra L; Rodriguez-Gil, Jorge L; Demichele, Angela; Chanock, Stephen J; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong; Huo, Dezheng; Zheng, Yonglan; Cox, Nancy J; Olopade, Olufunmilayo I; Ogundiran, Temidayo O; Adebamowo, Clement; Nathanson, Katherine L; Domchek, Susan M; Simon, Michael S; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M Cristina; Ambs, Stefan; Hutter, Carolyn M; Young, Alicia; Kooperberg, Charles; Peters, Ulrike; Rhie, Suhn K; Wan, Peggy; Sheng, Xin; Pooler, Loreall C; Van Den Berg, David J; Le Marchand, Loic; Kolonel, Laurence N; Henderson, Brian E; Haiman, Christopher A

    2013-01-01

    Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of >1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10(-6) and 10(-5) in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3 × 10(-6); rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5 × 10(-5)). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.

  17. West African and Amerindian ancestry and risk of myocardial infarction and metabolic syndrome in the Central Valley population of Costa Rica.

    PubMed

    Ruiz-Narváez, Edward A; Bare, Lance; Arellano, Andre; Catanese, Joseph; Campos, Hannia

    2010-06-01

    Genetic ancestry and environmental factors may contribute to the ethnic differences in risk of coronary heart disease (CHD), metabolic syndrome (MS) or its individual components. The population of the Central Valley of Costa Rica offers a unique opportunity to assess the role of genetic ancestry in these chronic diseases because it derived from the admixture of a relatively small number of founders of Southern European, Amerindian, and West African origin. We aimed to determine whether genetic ancestry is associated with risk of myocardial infarction (MI), MS and its individual components in the Central Valley of Costa Rica. We genotyped 39 ancestral informative markers in cases (n = 1,998) with a first non-fatal acute MI and population-based controls (n = 1,998) matched for age, sex, and area of residence, to estimate individual ancestry proportions. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using conditional (MI) and unconditional (MS and its components) logistic regression adjusting for relevant confounders. Mean individual ancestry proportions in cases and controls were 57.5 versus 57.8% for the Southern European, 38.4 versus 38.3% for the Amerindian and 4.1 versus 3.8% for the West African ancestry. Compared with Southern European ancestry, each 10% increase in West African ancestry was associated with a 29% increase in MI, OR (95% CI) = 1.29 (1.07, 1.56), and with a 30% increase on the risk of hypertension, OR (95% CI) = 1.30 (1.00, 1.70). Each 10% increase in Amerindian ancestry was associated with a 14% increase on the risk of MS, OR (95% CI) = 1.14 (1.00, 1.30), and 20% increase on the risk of impaired fasting glucose, OR (95% CI) = 1.20 (1.01, 1.42). These results show that the high variability of admixture proportions in the Central Valley population offers a unique opportunity to uncover the genetic basis of ethnic differences on the risk of disease.

  18. The Role of Adipose Tissue in Insulin Resistance in Women of African Ancestry

    PubMed Central

    Goedecke, Julia H.; Levitt, Naomi S.; Evans, Juliet; Ellman, Nicole; Hume, David John; Kotze, Liske; Tootla, Mehreen; Victor, Hendriena; Keswell, Dheshnie

    2013-01-01

    Women of African ancestry, particularly those living in industrialized countries, experience a disproportionately higher prevalence of type 2 diabetes (T2D) compared to their white counterparts. Similarly, obesity and insulin resistance, which are major risk factors for T2D, are greater in black compared to white women. The exact mechanisms underlying these phenomena are not known. This paper will focus on the role of adipose tissue biology. Firstly, the characteristic body fat distribution of women of African ancestry will be discussed, followed by the depot-specific associations with insulin resistance. Factors involved in adipose tissue biology and their relation to insulin sensitivity will then be explored, including the role of sex hormones, glucocorticoid metabolism, lipolysis and adipogenesis, and their consequent effects on adipose tissue hypoxia, oxidative stress, and inflammation. Finally the role of ectopic fat deposition will be discussed. The paper proposes directions for future research, in particular highlighting the need for longitudinal and/or intervention studies to better understand the mechanisms underlying the high prevalence of insulin resistance and T2D in women of African ancestry. PMID:23401754

  19. Bio science: genetic genealogy testing and the pursuit of African ancestry.

    PubMed

    Nelson, Alondra

    2008-10-01

    This paper considers the extent to which the geneticization of 'race' and ethnicity is the prevailing outcome of genetic testing for genealogical purposes. The decoding of the human genome precipitated a change of paradigms in genetics research, from an emphasis on genetic similarity to a focus on molecular-level differences among individuals and groups. This shift from lumping to splitting spurred ongoing disagreements among scholars about the significance of 'race' and ethnicity in the genetics era. I characterize these divergent perspectives as 'pragmatism' and 'naturalism'. Drawing upon ethnographic fieldwork and interviews, I argue that neither position fully accounts for how understandings of 'race' and ethnicity are being transformed with genetic genealogy testing. While there is some acquiescence to genetic thinking about ancestry, and by implication, 'race', among African-American and black British consumers of genetic genealogy testing, test-takers also adjudicate between sources of genealogical information and from these construct meaningful biographical narratives. Consumers engage in highly situated 'objective' and 'affiliative' self-fashioning, interpreting genetic test results in the context of their 'genealogical aspirations'. I conclude that issues of site, scale, and subjectification must be attended to if scholars are to understand whether and to what extent social identities are being transformed by recent developments in genetic science.

  20. Differences in vaginal microbiome in African American women versus women of European ancestry.

    PubMed

    Fettweis, Jennifer M; Brooks, J Paul; Serrano, Myrna G; Sheth, Nihar U; Girerd, Philippe H; Edwards, David J; Strauss, Jerome F; Jefferson, Kimberly K; Buck, Gregory A

    2014-10-01

    Women of European ancestry are more likely to harbour a Lactobacillus-dominated microbiome, whereas African American women are more likely to exhibit a diverse microbial profile. African American women are also twice as likely to be diagnosed with bacterial vaginosis and are twice as likely to experience preterm birth. The objective of this study was to further characterize and contrast the vaginal microbial profiles in African American versus European ancestry women. Through the Vaginal Human Microbiome Project at Virginia Commonwealth University, 16S rRNA gene sequence analysis was used to compare the microbiomes of vaginal samples from 1268 African American women and 416 women of European ancestry. The results confirmed significant differences in the vaginal microbiomes of the two groups and identified several taxa relevant to these differences. Major community types were dominated by Gardnerella vaginalis and the uncultivated bacterial vaginosis-associated bacterium-1 (BVAB1) that were common among African Americans. Moreover, the prevalence of multiple bacterial taxa that are associated with microbial invasion of the amniotic cavity and preterm birth, including Mycoplasma, Gardnerella, Prevotella and Sneathia, differed between the two ethnic groups. We investigated the contributions of intrinsic and extrinsic factors, including pregnancy, body mass index, diet, smoking and alcohol use, number of sexual partners, and household income, to vaginal community composition. Ethnicity, pregnancy and alcohol use correlated significantly with the relative abundance of bacterial vaginosis-associated species. Trends between microbial profiles and smoking and number of sexual partners were observed; however, these associations were not statistically significant. These results support and extend previous findings that there are significant differences in the vaginal microbiome related to ethnicity and demonstrate that these differences are pronounced even in healthy women.

  1. Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

    PubMed Central

    Lange, Leslie; Demerath, Ellen W.; Palmas, Walter; Wojczynski, Mary K.; Ellis, Jaclyn C.; Vitolins, Mara Z.; Liu, Simin; Papanicolaou, George J.; Irvin, Marguerite R.; Xue, Luting; Griffin, Paula J.; Nalls, Michael A.; Adeyemo, Adebowale; Liu, Jiankang; Li, Guo; Ruiz-Narvaez, Edward A.; Chen, Wei-Min; Chen, Fang; Henderson, Brian E.; Millikan, Robert C.; Ambrosone, Christine B.; Strom, Sara S.; Guo, Xiuqing; Andrews, Jeanette S.; Sun, Yan V.; Mosley, Thomas H.; Yanek, Lisa R.; Shriner, Daniel; Haritunians, Talin; Rotter, Jerome I.; Speliotes, Elizabeth K.; Smith, Megan; Rosenberg, Lynn; Mychaleckyj, Josyf; Nayak, Uma; Spruill, Ida; Garvey, W. Timothy; Pettaway, Curtis; Nyante, Sarah; Bandera, Elisa V.; Britton, Angela F.; Zonderman, Alan B.; Rasmussen-Torvik, Laura J.; Chen, Yii-Der Ida; Ding, Jingzhong; Lohman, Kurt; Kritchevsky, Stephen B.; Zhao, Wei; Peyser, Patricia A.; Kardia, Sharon L. R.; Kabagambe, Edmond; Broeckel, Ulrich; Chen, Guanjie; Zhou, Jie; Wassertheil-Smoller, Sylvia; Neuhouser, Marian L.; Rampersaud, Evadnie; Psaty, Bruce; Kooperberg, Charles; Manson, JoAnn E.; Kuller, Lewis H.; Ochs-Balcom, Heather M.; Johnson, Karen C.; Sucheston, Lara; Ordovas, Jose M.; Palmer, Julie R.; Haiman, Christopher A.; McKnight, Barbara; Howard, Barbara V.; Becker, Diane M.; Bielak, Lawrence F.; Liu, Yongmei; Allison, Matthew A.; Grant, Struan F. A.; Burke, Gregory L.; Patel, Sanjay R.; Schreiner, Pamela J.; Borecki, Ingrid B.; Evans, Michele K.; Taylor, Herman; Sale, Michele M.; Howard, Virginia; Carlson, Christopher S.; Rotimi, Charles N.; Cushman, Mary; Harris, Tamara B.; Reiner, Alexander P.; Cupples, L. Adrienne; North, Kari E.; Fox, Caroline S.

    2013-01-01

    Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce

  2. Socioeconomic Position, But Not African Genomic Ancestry, Is Associated With Blood Pressure in the Bambui-Epigen (Brazil) Cohort Study of Aging.

    PubMed

    Lima-Costa, M Fernanda; Mambrini, Juliana Vaz de Mello; Leite, Maria Lea Corrêa; Peixoto, Sérgio Viana; Firmo, Josélia Oliveira Araújo; Loyola Filho, Antônio Ignácio de; Gouveia, Mateus H; Leal, Thiago P; Pereira, Alexandre Costa; Macinko, James; Tarazona-Santos, Eduardo

    2016-02-01

    The study objective is to examine the role of African genome origin on baseline and 11-year blood pressure trajectories in community-based ethnoracially admixed older adults in Brazil. Data come from 1272 participants (aged ≥60 years) of the Bambui cohort study of aging during 11 years of follow-up. Outcome measures were systolic blood pressure, diastolic blood pressure, and hypertension control. Potential confounding variables were demographic characteristics, socioeconomic position (schooling and household income), and health indicators (smoking, sedentary lifestyle, high-density lipoprotein cholesterol, waist circumference, diabetes mellitus, and cardiovascular diseases), including antihypertensive drug use. We used 370 539 single-nucleotide polymorphisms to estimate each individual's African, European, and Native American trihybrid ancestry proportions. Median African, European, and Native American ancestry were 9.6%, 84.0%, and 5.3%, respectively. Among those with African ancestry, 59.4% came from East and 40.6% from West Africa. Baseline systolic and diastolic blood pressure, controlled hypertension, and their respective trajectories, were not significantly (P>0.05) associated with level (in quintiles) of African genomic ancestry. Similar results were found for West and East African subcontinental origins. Lower schooling level (<4 years versus higher) showed a significant and positive association with systolic blood pressure (Adjusted β=2.92; 95% confidence interval, 0.85-4.99). Lower monthly household income per capita (

  3. Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

    PubMed

    Zheng, Yonglan; Ogundiran, Temidayo O; Falusi, Adeyinka G; Nathanson, Katherine L; John, Esther M; Hennis, Anselm J M; Ambs, Stefan; Domchek, Susan M; Rebbeck, Timothy R; Simon, Michael S; Nemesure, Barbara; Wu, Suh-Yuh; Leske, Maria Cristina; Odetunde, Abayomi; Niu, Qun; Zhang, Jing; Afolabi, Chibuzor; Gamazon, Eric R; Cox, Nancy J; Olopade, Christopher O; Olopade, Olufunmilayo I; Huo, Dezheng

    2013-07-01

    Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11-1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09-1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08-1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1-q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16-1.27; P = 9.7 × 10(-16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.

  4. Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.

    PubMed

    Han, Ying; Rand, Kristin A; Hazelett, Dennis J; Ingles, Sue A; Kittles, Rick A; Strom, Sara S; Rybicki, Benjamin A; Nemesure, Barbara; Isaacs, William B; Stanford, Janet L; Zheng, Wei; Schumacher, Fredrick R; Berndt, Sonja I; Wang, Zhaoming; Xu, Jianfeng; Rohland, Nadin; Reich, David; Tandon, Arti; Pasaniuc, Bogdan; Allen, Alex; Quinque, Dominique; Mallick, Swapan; Notani, Dimple; Rosenfeld, Michael G; Jayani, Ranveer Singh; Kolb, Suzanne; Gapstur, Susan M; Stevens, Victoria L; Pettaway, Curtis A; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; John, Esther M; Murphy, Adam B; Signorello, Lisa B; Carpten, John; Leske, M Cristina; Wu, Suh-Yuh; Hennis, Anslem J M; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Witte, John S; Casey, Graham; Lubwama, Alex; Pooler, Loreall C; Sheng, Xin; Coetzee, Gerhard A; Cook, Michael B; Chanock, Stephen J; Stram, Daniel O; Watya, Stephen; Blot, William J; Conti, David V; Henderson, Brian E; Haiman, Christopher A

    2016-07-01

    The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

  5. Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Brazilian population with high African ancestry.

    PubMed

    do Rego Borges, Andrea; Sá, Jamile; Hoshi, Ryuichi; Viena, Camila Sane; Mariano, Lorena C; de Castro Veiga, Patricia; Medrado, Alena Peixoto; Machado, Renato Assis; de Aquino, Sibele Nascimento; Messetti, Ana Camila; Spritz, Richard A; Coletta, Ricardo D; Reis, Silvia R A

    2015-10-01

    Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is the most common orofacial birth defect, exhibiting variable prevalence around the world, often attributed to ethnic and environmental differences. Linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL ± P, mostly in European-derived or Asian populations. Genetic predisposition to NSCL ± P is ethnicity-dependent, and the genetic basis of susceptibility to NSCL ± P likely varies among populations. The population of Brazil is highly admixed, with highly variable ancestry; thus, the genetic determinants of NSCL ± P susceptibility may be quite different. This study tested association of 8 single-nucleotide polymorphisms (SNPs), previously identified by genome-wide studies in other populations, with NSCL ± P in a Brazilian population with high African ancestry. SNPs rs560426, rs642961, rs1530300, rs987525, rs3758249, rs7078160, rs17085106, and rs13041247 were genotyped in 293 Brazilian patients with NSCL ± P and 352 unaffected Brazilian controls. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphic markers to characterize genetic ancestry. The average African ancestry background was 31.1% for the NSCL ± P group and 36.7% for the control group. After adjustment for ancestry and multiple testing, the minor alleles of rs3758249 (OR: 1.58, 95% CI: 1.25-2.01, P = 0.0001) and rs7078160 (OR: 1.59, 95% CI: 1.21-2.07, P = 0.0002) were significantly associated with risk of NSCL ± P. Polymorphisms located in IRF6 (rs642961) and 8q24 (rs1530300 and rs987525) showed marginal associations in this Brazilian population with high African ancestry. These results indicate that rs3758249 at 9q22 and rs7078160 at 10q25.3 represent risk loci for NSCL ± P in the Brazilian population with high African ancestry.

  6. Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.

    PubMed

    Rand, Kristin A; Rohland, Nadin; Tandon, Arti; Stram, Alex; Sheng, Xin; Do, Ron; Pasaniuc, Bogdan; Allen, Alex; Quinque, Dominique; Mallick, Swapan; Le Marchand, Loic; Kaggwa, Sam; Lubwama, Alex; Stram, Daniel O; Watya, Stephen; Henderson, Brian E; Conti, David V; Reich, David; Haiman, Christopher A

    2016-01-15

    Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.

  7. Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk

    PubMed Central

    Rand, Kristin A.; Rohland, Nadin; Tandon, Arti; Stram, Alex; Sheng, Xin; Do, Ron; Pasaniuc, Bogdan; Allen, Alex; Quinque, Dominique; Mallick, Swapan; Le Marchand, Loic; Kaggwa, Sam; Lubwama, Alex; Stram, Daniel O.; Watya, Stephen; Henderson, Brian E.; Conti, David V.; Reich, David; Haiman, Christopher A.

    2016-01-01

    Prostate cancer is the most common non-skin cancer in males, with a ∼1.5–2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10−6) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10−5). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10−4) and GORAB (P = 2.3 × 10−4). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case–control or case–case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5–1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk. PMID:26604137

  8. Differential effects of stress and African ancestry on preterm birth and related traits among US born and immigrant Black mothers

    PubMed Central

    Tsai, Hui-Ju; Surkan, Pamela J.; Yu, Stella M.; Caruso, Deanna; Hong, Xiumei; Bartell, Tami R.; Wahl, Anastacia D.; Sampankanpanich, Claire; Reily, Anne; Zuckerman, Barry S.; Wang, Xiaobin

    2017-01-01

    Abstract Preterm birth (PTB, <37 weeks of gestation) is influenced by a wide range of environmental, genetic and psychosocial factors, and their interactions. However, the individual and joint effects of genetic factors and psychosocial stress on PTB have remained largely unexplored among U.S. born versus immigrant mothers. We studied 1121 African American women from the Boston Birth Cohort enrolled from 1998 to 2008. Regression-based analyses were performed to examine the individual and joint effects of genetic ancestry and stress (including lifetime stress [LS] and stress during pregnancy [PS]) on PTB and related traits among U.S. born and immigrant mothers. Significant associations between LS and PTB and related traits were found in the total study population and in immigrant mothers, including gestational age, birthweight, PTB, and spontaneous PTB; but no association was found in U.S. born mothers. Furthermore, significant joint associations of LS (or PS) and African ancestral proportion (AAP) on PTB were found in immigrant mothers, but not in U.S. born mothers. Although, overall, immigrant women had lower rates of PTB compared to U.S. born women, our study is one of the first to identify a subset of immigrant women could be at significantly increased risk of PTB and related outcomes if they have high AAP and are under high LS or PS. In light of the growing number of immigrant mothers in the U.S., our findings may have important clinical and public health implications. PMID:28151865

  9. Myosteatosis increases with aging and is associated with incident diabetes in African ancestry men

    PubMed Central

    Miljkovic, I; Kuipers, AL; Cvejkus, R; Bunker, CH; Patrick, AL; Gordon, CL; Zmuda, JM

    2015-01-01

    Objective Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes (T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse. Methods We examined longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis [inter-muscular fat (mm2) and skeletal muscle density as a measure of intra-muscular fat (mg/cm3)] in 1,515 Afro-Caribbean men aged 40+ years recruited without regard to their health status. Results During an average of 6.2 years of follow-up, we observed an age-related increase in inter-muscular fat and a decrease in skeletal muscle density (all P<0.0001), which remained significant in those who lost weight, gained weight, or remained weight-stable (all P<0.0001). In addition, muscle density loss accelerated with increasing age (P<0.0001). Increased inter-muscular fat during follow-up was associated with an increased incident risk of T2D independent of factors known to be associated with T2D (Odds ratios per 1-SD increase in inter-muscular fat=1.29; 95% CI=1.08-1.53). Conclusions Our findings suggest that both inter- and intra- muscular fat increase with advancing age and that inter-muscular fat contributes to development of T2D among African ancestry men. PMID:26694517

  10. Bernard-Soulier syndrome: common ancestry in two African American families with the GP Ib alpha Leu129Pro mutation.

    PubMed

    Antonucci, J V; Martin, E S; Hulick, P J; Joseph, A; Martin, S E

    2000-10-01

    Bernard-Soulier syndrome (BSs) is a rare bleeding disorder characterized by circulating giant platelets, thrombocytopenia, and a prolonged bleeding time. BSs usually has an autosomal recessive inheritance pattern, with a preponderance of Caucasian and Japanese ancestry when the ethnic background has been reported. Underlying this disorder of platelet function is a defect in the platelet glycoprotein (GP) Ib-IX-V complex, composed of four polypeptides, GP Ib alpha, GP Ib beta, GP IX, and GP V. Molecular characterization of individuals with BSs has identified mutations in the GP Ib alpha, GP Ib beta, and GP IX genes responsible for the expressed phenotype. In this study, we report a family of African-American descent, with autosomal recessive BSs showing a point mutation in codon 129 of the GP Ib alpha gene. This mutation, CTC:wild-type to CCC:mutant, is similar to that of another African American family where the resulting leucine to proline substitution in the 5(th) leucine-rich repeat of GP Ib alpha is responsible for the observed BSs phenotype. Comparison of the intragenic polymorphisms of GP Ib alpha, as well as microsatellite markers in a 17.5 cM region of chromosome 17p12 that contains the GP Ib alpha gene, suggests that, although socially unrelated, the Leu129Pro mutation in these two families has a common founder.

  11. OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans

    PubMed Central

    Soares, Pedro; Garcia, Gissel; Perez, Ana B.; Aguirre, Eglys; Cavadas, Bruno; Regnault, Béatrice; Alvarez, Mayling; Ruiz, Didye; Guzman, Maria G.

    2017-01-01

    Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease. PMID:28241052

  12. Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

    PubMed Central

    Emeville, Elise; Ferdinand, Séverine; Punga, Augustin; Lufuma, Simon; Blanchet, Pascal; Romana, Marc; Multigner, Luc

    2016-01-01

    Background Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer. Objective We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry. Methods In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations. Conclusions These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry. PMID:27074016

  13. Single-Nucleotide Polymorphisms in LPA Explain Most of the Ancestry-Specific Variation in Lp(a) Levels in African Americans

    PubMed Central

    Lawson, Kim; Kao, W. H. Linda; Reich, David; Tandon, Arti; Akylbekova, Ermeg; Patterson, Nick; Mosley, Thomas H.; Boerwinkle, Eric; Taylor, Herman A.

    2011-01-01

    Lipoprotein(a) (Lp(a)) is an important causal cardiovascular risk factor, with serum Lp(a) levels predicting atherosclerotic heart disease and genetic determinants of Lp(a) levels showing association with myocardial infarction. Lp(a) levels vary widely between populations, with African-derived populations having nearly 2-fold higher Lp(a) levels than European Americans. We investigated the genetic basis of this difference in 4464 African Americans from the Jackson Heart Study (JHS) using a panel of up to 1447 ancestry informative markers, allowing us to accurately estimate the African ancestry proportion of each individual at each position in the genome. In an unbiased genome-wide admixture scan for frequency-differentiated genetic determinants of Lp(a) level, we found a convincing peak (LOD = 13.6) at 6q25.3, which spans the LPA locus. Dense fine-mapping of the LPA locus identified a number of strongly associated, common biallelic SNPs, a subset of which can account for up to 7% of the variation in Lp(a) level, as well as >70% of the African-European population differences in Lp(a) level. We replicated the association of the most strongly associated SNP, rs9457951 (p = 6×10−22, 27% change in Lp(a) per allele, ∼5% of Lp(a) variance explained in JHS), in 1,726 African Americans from the Dallas Heart Study and found an even stronger association after adjustment for the kringle(IV) repeat copy number. Despite the strong association with Lp(a) levels, we find no association of any LPA SNP with incident coronary heart disease in 3,225 African Americans from the Atherosclerosis Risk in Communities Study. PMID:21283670

  14. Population genetics models of local ancestry.

    PubMed

    Gravel, Simon

    2012-06-01

    Migrations have played an important role in shaping the genetic diversity of human populations. Understanding genomic data thus requires careful modeling of historical gene flow. Here we consider the effect of relatively recent population structure and gene flow and interpret genomes of individuals that have ancestry from multiple source populations as mosaics of segments originating from each population. This article describes general and tractable models for local ancestry patterns with a focus on the length distribution of continuous ancestry tracts and the variance in total ancestry proportions among individuals. The models offer improved agreement with Wright-Fisher simulation data when compared to the state-of-the art and can be used to infer time-dependent migration rates from multiple populations. Considering HapMap African-American (ASW) data, we find that a model with two distinct phases of "European" gene flow significantly improves the modeling of both tract lengths and ancestry variances.

  15. Association of Aldosterone Synthase Polymorphism (CYP11B2 -344T>C) and Genetic Ancestry with Atrial Fibrillation and Serum Aldosterone in African Americans with Heart Failure

    PubMed Central

    Bress, Adam; Han, Jin; Patel, Shitalben R.; Desai, Ankit A.; Mansour, Ibrahim; Groo, Vicki; Progar, Kristin; Shah, Ebony; Stamos, Thomas D.; Wing, Coady; Garcia, Joe G. N.; Kittles, Rick; Cavallari, Larisa H.

    2013-01-01

    The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determined using 105 autosomal ancestry informative markers. In a sub-set of patients (n = 126), serum was also collected for determination of circulating aldosterone. The CYP11B2 −344C allele frequency was 18% among the study population, and 19% of patients had AF. Multiple logistic regression revealed that the CYP11B2 −344CC genotype was a significant independent predictor of AF (OR 12.7, 95% CI 1.60–98.4, p = 0.0150, empirical p = 0.011) while holding multiple clinical factors, left atrial size, and percent European ancestry constant. Serum aldosterone was significantly higher among patients with AF (p = 0.036), whereas increased West African ancestry was inversely correlated with serum aldosterone (r = −0.19, p = 0.037). The CYP11B2 −344CC genotype was also overrepresented among patients with extreme aldosterone elevation (≥90th percentile, p = 0.0145). In this cohort of African Americans with chronic ambulatory heart failure, the CYP11B2 −344T>C genotype was a significant independent predictor of AF while holding clinical, echocardiographic predictors, and genetic ancestry constant. In addition, increased West African ancestry was associated with decreased serum aldosterone levels, potentially providing an explanation for the lower risk for AF observed among African Americans. PMID:23936266

  16. PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

    PubMed Central

    Adler, Adam; Chung, Sharon A.; Kaufman, Kenneth M.; Kelly, Jennifer A.; Glenn, Stuart B.; Guthridge, Joel M.; Scofield, Robert H.; Kimberly, Robert P.; Brown, Elizabeth E.; Alarcón, Graciela S.; Edberg, Jeffrey C.; Kim, Jae-Hoon; Choi, Jiyoung; Ramsey-Goldman, Rosalind; Petri, Michelle A.; Reveille, John D.; Vilá, Luis M.; Boackle, Susan A.; Freedman, Barry I.; Tsao, Betty P.; Langefeld, Carl D.; Vyse, Timothy J.; Jacob, Chaim O.; Pons-Estel, Bernardo; Niewold, Timothy B.; Moser Sivils, Kathy L.; Merrill, Joan T.; Anaya, Juan-Manuel; Gilkeson, Gary S.; Gaffney, Patrick M.; Bae, Sang-Cheol; Alarcón-Riquelme, Marta E.; Harley, John B.; Criswell, Lindsey A.; James, Judith A.; Nath, Swapan K.

    2013-01-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7×10−9, OR = 1.40 (95% CI = 1.25–1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67–0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7×10−5, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with

  17. PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical sub-phenotypes.

    PubMed

    Namjou, Bahram; Kim-Howard, Xana; Sun, Celi; Adler, Adam; Chung, Sharon A; Kaufman, Kenneth M; Kelly, Jennifer A; Glenn, Stuart B; Guthridge, Joel M; Scofield, Robert H; Kimberly, Robert P; Brown, Elizabeth E; Alarcón, Graciela S; Edberg, Jeffrey C; Kim, Jae-Hoon; Choi, Jiyoung; Ramsey-Goldman, Rosalind; Petri, Michelle A; Reveille, John D; Vilá, Luis M; Boackle, Susan A; Freedman, Barry I; Tsao, Betty P; Langefeld, Carl D; Vyse, Timothy J; Jacob, Chaim O; Pons-Estel, Bernardo; Niewold, Timothy B; Moser Sivils, Kathy L; Merrill, Joan T; Anaya, Juan-Manuel; Gilkeson, Gary S; Gaffney, Patrick M; Bae, Sang-Cheol; Alarcón-Riquelme, Marta E; Harley, John B; Criswell, Lindsey A; James, Judith A; Nath, Swapan K

    2013-01-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7 × 10(-9), OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7 × 10(-5), OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs

  18. Genome-Wide DNA Methylation in Mixed Ancestry Individuals with Diabetes and Prediabetes from South Africa

    PubMed Central

    Pheiffer, Carmen; Humphries, Stephen E.; Gamieldien, Junaid; Erasmus, Rajiv T.

    2016-01-01

    Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings. PMID:27555869

  19. Bight of Benin: a Maternal Perspective of Four Beninese Populations and their Genetic Implications on the American Populations of African Ancestry.

    PubMed

    Primativo, Giuseppina; Ottoni, Claudio; Biondi, Gianfranco; Serafino, Sara; Martínez-Labarga, Cristina; Larmuseau, Maarten H D; Scardi, Michele; Decorte, Ronny; Rickards, Olga

    2017-03-01

    The understanding of the first movements of the ancestral populations within the African continent is still unclear, particularly in West Africa, due to several factors that have shaped the African genetic pool across time. To improve the genetic representativeness of the Beninese population and to better understand the patterns of human settlement inside West Africa and the dynamics of peopling of the Democratic Republic of Benin, we analyzed the maternal genetic variation of 193 Beninese individuals belonging to Bariba, Berba, Dendi, and Fon populations. Results support the oral traditions indicating that the western neighbouring populations have been the ancestors of the first Beninese populations, and the extant genetic structure of the Beninese populations is most likely the result of admixture between populations from neighbouring countries and native people. The present findings highlight how the Beninese populations contributed to the gene pool of the extant populations of some American populations of African ancestry. This strengthens the hypothesis that the Bight of Benin was not only an assembly point for the slave trade during the Trans-Atlantic Slave Trade but also an important slave trapping area.

  20. Dissecting linkage disequilibrium in African-American genomes: roles of markers and individuals.

    PubMed

    Xu, Shuhua; Huang, Wei; Wang, Haifeng; He, Yungang; Wang, Ying; Wang, Yi; Qian, Ji; Xiong, Momiao; Jin, Li

    2007-09-01

    Substantial increases of linkage disequilibrium (LD) both in magnitude and in range have been observed in recently admixed populations such as African-American (AfA). On the other hand, it has also been shown that LD in AfAs was very similar to that of African. In this study, we attempted to resolve these contradicting observations by conducting a systematic examination of the LD structure in AfAs by genotyping a sample of AfA individuals at 24,341 single nucleotide polymorphisms (SNPs) spanning almost the entire chromosome 21, with an average density of 1.5 kb/SNP. The overall LD in AfAs is similar to that in African populations and much less than that in European populations. Even when the ancestry-informative markers (AIMs) were used, extended LD in AfA was found to be limited to certain magnitude range (0.2 < or = r(2) < or = 0.8) and certain distance range, that is, between-marker distance more than 200 kb. Furthermore, the inclusion of AfA individuals with predominant African ancestry was found to reduce the overall magnitude of LD. Elevation of LD in the AfA population, compared with its parental populations, can only be observed at the markers with large allele frequency differences between 2 parental populations at limited scenario. AfA individuals of wholly African ancestry contribute little to the extended LD in the AfA population, and further genotyping or association analysis conducted using only admixed individuals may lead to higher statistical power and possibly reduced cost.

  1. African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans.

    PubMed

    Behar, Doron M; Rosset, Saharon; Tzur, Shay; Selig, Sara; Yudkovsky, Guennady; Bercovici, Sivan; Kopp, Jeffrey B; Winkler, Cheryl A; Nelson, George W; Wasser, Walter G; Skorecki, Karl

    2010-05-01

    Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.

  2. Determining the Effects and Challenges of Incorporating Genetic Testing into Primary Care Management of Hypertensive Patients with African Ancestry

    PubMed Central

    Abul-Husn, NS; Ellis, S; Ramos, MA; Negron, R; Suprun, M; Zinberg, RE; Sabin, T; Hauser, D; Calman, N; Bagiella, E; Bottinger, EP

    2016-01-01

    People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities. GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic risk information into primary care. Hypertensive, non-diabetic, adults with self-reported African ancestry, without kidney dysfunction, are recruited from diverse clinical settings and randomized to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control). Providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff return APOL1 results to patients and provide low-literacy educational materials. Real-time clinical decision support tools alert clinicians of their patients’ APOL1 results and associated risk status at the point of care. Our academic-community-clinical partnership designed a study to generate information about the impact of genetic risk information on patient care (blood pressure and renal surveillance) and on patient and provider knowledge, attitudes, beliefs, and behaviors. GUARDD will help establish the effective implementation of APOL1 risk-informed management of hypertensive patients at high risk of CKD, and will provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices. It will also add to the important dialogue about factors that contribute to and may help eliminate racial disparities in kidney disease. PMID:26747051

  3. Color and genomic ancestry in Brazilians

    PubMed Central

    Parra, Flavia C.; Amado, Roberto C.; Lambertucci, José R.; Rocha, Jorge; Antunes, Carlos M.; Pena, Sérgio D. J.

    2003-01-01

    This work was undertaken to ascertain to what degree the physical appearance of a Brazilian individual was predictive of genomic African ancestry. Using a panel of 10 population-specific alleles, we assigned to each person an African ancestry index (AAI). The procedure was able to tell apart, with no overlaps, 20 males from northern Portugal from 20 males from São Tomé Island on the west coast of Africa. We also tested 10 Brazilian Amerindians and observed that their AAI values fell in the same range as the Europeans. Finally, we studied two different Brazilian population samples. The first consisted of 173 individuals from a rural Southeastern community, clinically classified according to their Color (white, black, or intermediate) with a multivariate evaluation based on skin pigmentation in the medial part of the arm, hair color and texture, and the shape of the nose and lips. In contrast to the clear-cut results with the African and European samples, our results showed large variances and extensive overlaps among the three Color categories. We next embarked on a study of 200 unrelated Brazilian white males who originated from cosmopolitan centers of the four major geographic regions of the country. The results showed AAI values intermediate between Europeans and Africans, even in southern Brazil, a region predominantly peopled by European immigrants. Our data suggest that in Brazil, at an individual level, color, as determined by physical evaluation, is a poor predictor of genomic African ancestry, estimated by molecular markers. PMID:12509516

  4. Genome-wide patterns of population structure and admixture in West Africans and African Americans.

    PubMed

    Bryc, Katarzyna; Auton, Adam; Nelson, Matthew R; Oksenberg, Jorge R; Hauser, Stephen L; Williams, Scott; Froment, Alain; Bodo, Jean-Marie; Wambebe, Charles; Tishkoff, Sarah A; Bustamante, Carlos D

    2010-01-12

    Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (n = 365) and individuals with ancestry from West Africa (n = 203 from 12 populations) and Europe (n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th-75th percentiles: 11.6-27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade.

  5. Genome-wide ancestry of 17th-century enslaved Africans from the Caribbean.

    PubMed

    Schroeder, Hannes; Ávila-Arcos, María C; Malaspinas, Anna-Sapfo; Poznik, G David; Sandoval-Velasco, Marcela; Carpenter, Meredith L; Moreno-Mayar, José Víctor; Sikora, Martin; Johnson, Philip L F; Allentoft, Morten Erik; Samaniego, José Alfredo; Haviser, Jay B; Dee, Michael W; Stafford, Thomas W; Salas, Antonio; Orlando, Ludovic; Willerslev, Eske; Bustamante, Carlos D; Gilbert, M Thomas P

    2015-03-24

    Between 1500 and 1850, more than 12 million enslaved Africans were transported to the New World. The vast majority were shipped from West and West-Central Africa, but their precise origins are largely unknown. We used genome-wide ancient DNA analyses to investigate the genetic origins of three enslaved Africans whose remains were recovered on the Caribbean island of Saint Martin. We trace their origins to distinct subcontinental source populations within Africa, including Bantu-speaking groups from northern Cameroon and non-Bantu speakers living in present-day Nigeria and Ghana. To our knowledge, these findings provide the first direct evidence for the ethnic origins of enslaved Africans, at a time for which historical records are scarce, and demonstrate that genomic data provide another type of record that can shed new light on long-standing historical questions.

  6. Genome-wide ancestry of 17th-century enslaved Africans from the Caribbean

    PubMed Central

    Schroeder, Hannes; Ávila-Arcos, María C.; Malaspinas, Anna-Sapfo; Sandoval-Velasco, Marcela; Carpenter, Meredith L.; Moreno-Mayar, José Víctor; Sikora, Martin; Johnson, Philip L. F.; Allentoft, Morten Erik; Samaniego, José Alfredo; Haviser, Jay B.; Dee, Michael W.; Stafford, Thomas W.; Salas, Antonio; Orlando, Ludovic; Willerslev, Eske; Bustamante, Carlos D.; Gilbert, M. Thomas P.

    2015-01-01

    Between 1500 and 1850, more than 12 million enslaved Africans were transported to the New World. The vast majority were shipped from West and West-Central Africa, but their precise origins are largely unknown. We used genome-wide ancient DNA analyses to investigate the genetic origins of three enslaved Africans whose remains were recovered on the Caribbean island of Saint Martin. We trace their origins to distinct subcontinental source populations within Africa, including Bantu-speaking groups from northern Cameroon and non-Bantu speakers living in present-day Nigeria and Ghana. To our knowledge, these findings provide the first direct evidence for the ethnic origins of enslaved Africans, at a time for which historical records are scarce, and demonstrate that genomic data provide another type of record that can shed new light on long-standing historical questions. PMID:25755263

  7. Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry.

    PubMed

    Yeh, E; Kimura, L; Errera, F I V; Angeli, C B; Mingroni-Netto, R C; Silva, M E R; Canani, L H S; Passos-Bueno, M R

    2008-06-01

    Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 +/- 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.

  8. Influence of environmental and genetic factors on CYP1A2 activity in individuals of South Asian and European ancestry.

    PubMed

    Perera, V; Gross, A S; McLachlan, A J

    2012-10-01

    The drug-metabolizing enzyme CYP1A2 contributes to the metabolism of a number of commonly used medicines and displays wide interindividual variability. The aim of this study was to investigate CYP1A2 activity in a population of South Asian ancestry and compare it with a population of European ancestry. CYP1A2 activity was determined using the 4 h paraxanthine/caffeine saliva concentration ratio following a 100-mg oral dose of caffeine in healthy individuals of South Asian (n = 166) and European (n = 166) ancestry. Participants were surveyed for extrinsic ethnic factors and genotyped for polymorphisms in CYP1A2 and related genes. Significantly lower CYP1A2 activity was observed in South Asian participants (median: 0.42; range: 0.10-1.06) as compared with European participants (0.54; 0.12-1.64) (P < 0.01). Multiple linear regression indicated that 41% of the variability in CYP1A2 activity could be explained by the diet, lifestyle, and genetic factors studied.

  9. Population Genetic Inference from Personal Genome Data: Impact of Ancestry and Admixture on Human Genomic Variation

    PubMed Central

    Kidd, Jeffrey M.; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D.; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F.; Peckham, Heather E.; Omberg, Larsson; Bormann Chung, Christina A.; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G.; Russell, Archie; Reynolds, Andy; Clark, Andrew G.; Reese, Martin G.; Lincoln, Stephen E.; Butte, Atul J.; De La Vega, Francisco M.; Bustamante, Carlos D.

    2012-01-01

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas—70% of the European ancestry in today’s African Americans dates back to European gene flow happening only 7–8 generations ago. PMID:23040495

  10. The Relationship between Native American Ancestry, Body Mass Index and Diabetes Risk among Mexican-Americans.

    PubMed

    Hu, Hao; Huff, Chad D; Yamamura, Yuko; Wu, Xifeng; Strom, Sara S

    2015-01-01

    Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with <20% Native American ancestry were 2.5 times more likely to be severely obese compared to those with >80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies.

  11. Association of Lipopolysaccharide-Binding Protein With Aging-Related Adiposity Change and Prediabetes Among African Ancestry Men

    PubMed Central

    Zmuda, Joseph M.; Kuipers, Allison L.; Nestlerode, Cara S.; Evans, Rhobert W.; Bunker, Clareann H.; Patrick, Alan L.

    2016-01-01

    OBJECTIVE Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years). RESEARCH DESIGN AND METHODS We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ˜6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP. RESULTS LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02–2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067). CONCLUSIONS LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity. PMID:26721818

  12. The genetic structure and history of Africans and African Americans.

    PubMed

    Tishkoff, Sarah A; Reed, Floyd A; Friedlaender, Françoise R; Ehret, Christopher; Ranciaro, Alessia; Froment, Alain; Hirbo, Jibril B; Awomoyi, Agnes A; Bodo, Jean-Marie; Doumbo, Ogobara; Ibrahim, Muntaser; Juma, Abdalla T; Kotze, Maritha J; Lema, Godfrey; Moore, Jason H; Mortensen, Holly; Nyambo, Thomas B; Omar, Sabah A; Powell, Kweli; Pretorius, Gideon S; Smith, Michael W; Thera, Mahamadou A; Wambebe, Charles; Weber, James L; Williams, Scott M

    2009-05-22

    Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies.

  13. Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.

    PubMed

    Chen, Li-Shiun; Saccone, Nancy L; Culverhouse, Robert C; Bracci, Paige M; Chen, Chien-Hsiun; Dueker, Nicole; Han, Younghun; Huang, Hongyan; Jin, Guangfu; Kohno, Takashi; Ma, Jennie Z; Przybeck, Thomas R; Sanders, Alan R; Smith, Jennifer A; Sung, Yun Ju; Wenzlaff, Angie S; Wu, Chen; Yoon, Dankyu; Chen, Ying-Ting; Cheng, Yu-Ching; Cho, Yoon Shin; David, Sean P; Duan, Jubao; Eaton, Charles B; Furberg, Helena; Goate, Alison M; Gu, Dongfeng; Hansen, Helen M; Hartz, Sarah; Hu, Zhibin; Kim, Young Jin; Kittner, Steven J; Levinson, Douglas F; Mosley, Thomas H; Payne, Thomas J; Rao, D C; Rice, John P; Rice, Treva K; Schwantes-An, Tae-Hwi; Shete, Sanjay S; Shi, Jianxin; Spitz, Margaret R; Sun, Yan V; Tsai, Fuu-Jen; Wang, Jen C; Wrensch, Margaret R; Xian, Hong; Gejman, Pablo V; He, Jiang; Hunt, Steven C; Kardia, Sharon L; Li, Ming D; Lin, Dongxin; Mitchell, Braxton D; Park, Taesung; Schwartz, Ann G; Shen, Hongbing; Wiencke, John K; Wu, Jer-Yuarn; Yokota, Jun; Amos, Christopher I; Bierut, Laura J

    2012-05-01

    Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.25-1.42, P = 1.1 × 10(-17) in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments.

  14. Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry

    PubMed Central

    Demirci, F. Yesim; Wang, Xingbin; Kelly, Jennifer A.; Morris, David L.; Barmada, M. Michael; Feingold, Eleanor; Kao, Amy H.; Sivils, Kathy L.; Bernatsky, Sasha; Pineau, Christian; Clarke, Ann; Ramsey-Goldman, Rosalind; Vyse, Timothy J.; Gaffney, Patrick M.; Manzi, Susan; Kamboh, M. Ilyas

    2016-01-01

    Objective Genome-wide association studies (GWASs) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high-density genotyping platforms. Follow-up studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in European-descent subjects. Here we report the results of a multi-stage study that we performed to identify novel SLE loci. Methods In Stage 1, we conducted a new GWAS of SLE in a North American case-control sample of European ancestry (n=1,166) genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. In Stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta-analysis using an additional dataset of European-descent subjects (>2,500 individuals), followed by replication of top meta-analysis findings in another dataset of European-descent subjects (>10,000 individuals) in Stage 3. Results As expected, our GWAS revealed most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed genome-wide significance threshold (P<5×10−8). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also supported in Stage 1 discovery sample and strongest signals were observed at 2q32/STAT4 (P=3.6×10−7) and at 8p23/BLK (P=8.1×10−6). Stage 2 meta-analyses identified a new genome-wide significant SLE locus at 12q12 (meta P=3.1×10−8), which was replicated in Stage 3. Conclusion Our multi-stage study identified and replicated a new SLE locus that warrants further follow-up in additional studies. Publicly available databases suggest that this new SLE signal falls within a functionally relevant genomic region and near biologically important genes. PMID:26316170

  15. MixFit: Methodology for Computing Ancestry-Related Genetic Scores at the Individual Level and Its Application to the Estonian and Finnish Population Studies

    PubMed Central

    Leitsalu, Liis; Fischer, Krista; Nuotio, Marja-Liisa; Esko, Tõnu; Boomsma, Dorothea Irene; Kyvik, Kirsten Ohm; Spector, Tim D.; Perola, Markus; Metspalu, Andres

    2017-01-01

    Ancestry information at the individual level can be a valuable resource for personalized medicine, medical, demographical and history research, as well as for tracing back personal history. We report a new method for quantitatively determining personal genetic ancestry based on genome-wide data. Numerical ancestry component scores are assigned to individuals based on comparisons with reference populations. These comparisons are conducted with an existing analytical pipeline making use of genotype phasing, similarity matrix computation and our addition—multidimensional best fitting by MixFit. The method is demonstrated by studying Estonian and Finnish populations in geographical context. We show the main differences in the genetic composition of these otherwise close European populations and how they have influenced each other. The components of our analytical pipeline are freely available computer programs and scripts one of which was developed in house (available at: www.geenivaramu.ee/en/tools/mixfit). PMID:28107396

  16. The birth prevalence of PKU in populations of European, South Asian and sub-Saharan African ancestry living in South East England.

    PubMed

    Hardelid, P; Cortina-Borja, M; Munro, A; Jones, H; Cleary, M; Champion, M P; Foo, Y; Scriver, C R; Dezateux, C

    2008-01-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism (OMIM 261600). Treatment with a low-phenylalanine diet following early ascertainment by newborn screening prevents impaired cognitive development, the major disease phenotype in PKU. The overall birth prevalence of PKU in European, Chinese and Korean populations is approximately 1/10,000. Since the human PAH locus contains PKU-causing alleles and polymorphic core haplotypes that describe and corroborate an out-of-Africa range expansion in modern human populations, it is of interest to know the prevalence of PKU in different ethnic groups with diverse geographical origin. We estimated PKU prevalence in South East England, where a sizeable proportion of the population are of Sub-Saharan African or South Asian ancestry. Over the period 1994 to 2004 167 children were diagnosed with PKU. Using birth registration and census data to derive denominators, PKU birth prevalence per 10,000 live births (95% Bayesian credible intervals) was estimated to be 1.14 (0.96-1.33) among white, 0.11 (0.02-0.37) among black, and 0.29 (0.10-0.63) among Asian ethnic groups. This suggests that PKU is up to an order of magnitude less prevalent in populations with Sub-Saharan African and South Asian ancestry that have migrated to the UK.

  17. Ancestry variation and footprints of natural selection along the genome in Latin American populations.

    PubMed

    Deng, Lian; Ruiz-Linares, Andrés; Xu, Shuhua; Wang, Sijia

    2016-02-18

    Latin American populations stem from the admixture of Europeans, Africans and Native Americans, which started over 400 years ago and had lasted for several centuries. Extreme deviation over the genome-wide average in ancestry estimations at certain genomic locations could reflect recent natural selection. We evaluated the distribution of ancestry estimations using 678 genome-wide microsatellite markers in 249 individuals from 13 admixed populations across Latin America. We found significant deviations in ancestry estimations including three locations with more than 3.5 times standard deviations from the genome-wide average: an excess of European ancestry at 1p36 and 14q32, and an excess of African ancestry at 6p22. Using simulations, we could show that at least the deviation at 6p22 was unlikely to result from genetic drift alone. By applying different linguistic groups as well as the most likely ancestral Native American populations as the ancestry, we showed that the choice of Native American ancestry could affect the local ancestry estimation. However, the signal at 6p22 consistently appeared in most of the analyses using various ancestral groups. This study provided important insights for recent natural selection in the context of the unique history of the New World and implications for disease mapping.

  18. Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.

    PubMed

    Huo, Dezheng; Feng, Ye; Haddad, Stephen; Zheng, Yonglan; Yao, Song; Han, Yoo-Jeong; Ogundiran, Temidayo O; Adebamowo, Clement; Ojengbede, Oladosu; Falusi, Adeyinka G; Zheng, Wei; Blot, William; Cai, Qiuyin; Signorello, Lisa; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Deming, Sandra L; Rodriguez-Gil, Jorge L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara E; Bensen, Jeannette T; Simon, Michael S; Hennis, Anselm; Nemesure, Barbara; Leske, M Cristina; Ambs, Stefan; Chen, Lin S; Qian, Frank; Gamazon, Eric R; Lunetta, Kathryn L; Cox, Nancy J; Chanock, Stephen J; Kolonel, Laurence N; Olshan, Andrew F; Ambrosone, Christine B; Olopade, Olufunmilayo I; Palmer, Julie R; Haiman, Christopher A

    2016-09-04

    Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 (-)  (8)). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 (-)  (10)) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 (-)  (8)) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

  19. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

    PubMed Central

    Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

    2015-01-01

    Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

  20. The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions

    PubMed Central

    Magalhães da Silva, Thiago; Sandhya Rani, M R; de Oliveira Costa, Gustavo Nunes; Figueiredo, Maria A; Melo, Paulo S; Nascimento, João F; Molyneaux, Neil D; Barreto, Maurício L; Reis, Mitermayer G; Teixeira, M Glória; Blanton, Ronald E

    2015-01-01

    The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of ‘race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3–5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry. PMID:25293718

  1. Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry.

    PubMed

    Quan, Lei; Gong, Zhihong; Yao, Song; Bandera, Elisa V; Zirpoli, Gary; Hwang, Helena; Roberts, Michelle; Ciupak, Gregory; Davis, Warren; Sucheston, Lara; Pawlish, Karen; Bovbjerg, Dana H; Jandorf, Lina; Cabasag, Citadel; Coignet, Jean-Gabriel; Ambrosone, Christine B; Hong, Chi-Chen

    2014-03-15

    Disparities in breast cancer biology are evident between American women of African ancestry (AA) and European ancestry (EA) and may be due, in part, to differences in immune function. To assess the potential role of constitutional host immunity on breast carcinogenesis, we tested associations between breast cancer risk and 47 single nucleotide polymorphisms (SNPs) in 26 cytokine-related genes of the adaptive immune system using 650 EA (n = 335 cases) and 864 AA (n = 458 cases) women from the Women's Circle of Health Study (WCHS). With additional participant accrual to the WCHS, promising SNPs from the initial analysis were evaluated in a larger sample size (1,307 EAs and 1,365 AAs). Multivariate logistic regression found SNPs in genes important for T helper type 1 (Th1) immunity (IFNGR2 rs1059293, IL15RA rs2296135, LTA rs1041981), Th2 immunity (IL4R rs1801275), and T regulatory cell-mediated immunosuppression (TGFB1 rs1800469) associated with breast cancer risk, mainly among AAs. The combined effect of these five SNPs was highly significant among AAs (P-trend = 0.0005). When stratified by estrogen receptor (ER) status, LTA rs1041981 was associated with ER-positive breast cancers among EAs and marginally among AAs. Only among AA women, IL15 rs10833 and IL15RA rs2296135 were associated with ER-positive tumors, and IL12RB1 rs375947, IL15 rs10833 and TGFB1 rs1800469 were associated with ER-negative tumors. Our study systematically identified genetic variants in the adaptive immune response pathway associated with breast cancer risk, which appears to differ by ancestry groups, menopausal status and ER status.

  2. Outlining the Ancestry Landscape of Colombian Admixed Populations.

    PubMed

    Ossa, Humberto; Aquino, Juliana; Pereira, Rui; Ibarra, Adriana; Ossa, Rafael H; Pérez, Luz Adriana; Granda, Juan David; Lattig, Maria Claudia; Groot, Helena; Fagundes de Carvalho, Elizeu; Gusmão, Leonor

    2016-01-01

    The ancestry of the Colombian population comprises a large number of well differentiated Native communities belonging to diverse linguistic groups. In the late fifteenth century, a process of admixture was initiated with the arrival of the Europeans, and several years later, Africans also became part of the Colombian population. Therefore, the genepool of the current Colombian population results from the admixture of Native Americans, Europeans and Africans. This admixture occurred differently in each region of the country, producing a clearly stratified population. Considering the importance of population substructure in both clinical and forensic genetics, we sought to investigate and compare patterns of genetic ancestry in Colombia by studying samples from Native and non-Native populations living in its 5 continental regions: the Andes, Caribe, Amazonia, Orinoquía, and Pacific regions. For this purpose, 46 AIM-Indels were genotyped in 761 non-related individuals from current populations. Previously published genotype data from 214 Colombian Natives from five communities were used for population comparisons. Significant differences were observed between Native and non-Native populations, among non-Native populations from different regions and among Native populations from different ethnic groups. The Pacific was the region with the highest African ancestry, Amazonia harboured the highest Native ancestry and the Andean and Orinoquían regions showed the highest proportion of European ancestry. The Andean region was further sub-divided into 6 sub-regions: North East, Central West, Central East, West, South West and South East. Among these regions, the South West region showed a significantly lower European admixture than the other regions. Hardy-Weinberg equilibrium and variance values of ancestry among individuals within populations showed a potential stratification of the Pacific population.

  3. Outlining the Ancestry Landscape of Colombian Admixed Populations

    PubMed Central

    Ossa, Humberto; Aquino, Juliana; Pereira, Rui; Ibarra, Adriana; Ossa, Rafael H; Pérez, Luz Adriana; Granda, Juan David; Lattig, Maria Claudia; Groot, Helena; Fagundes de Carvalho, Elizeu; Gusmão, Leonor

    2016-01-01

    The ancestry of the Colombian population comprises a large number of well differentiated Native communities belonging to diverse linguistic groups. In the late fifteenth century, a process of admixture was initiated with the arrival of the Europeans, and several years later, Africans also became part of the Colombian population. Therefore, the genepool of the current Colombian population results from the admixture of Native Americans, Europeans and Africans. This admixture occurred differently in each region of the country, producing a clearly stratified population. Considering the importance of population substructure in both clinical and forensic genetics, we sought to investigate and compare patterns of genetic ancestry in Colombia by studying samples from Native and non-Native populations living in its 5 continental regions: the Andes, Caribe, Amazonia, Orinoquía, and Pacific regions. For this purpose, 46 AIM-Indels were genotyped in 761 non-related individuals from current populations. Previously published genotype data from 214 Colombian Natives from five communities were used for population comparisons. Significant differences were observed between Native and non-Native populations, among non-Native populations from different regions and among Native populations from different ethnic groups. The Pacific was the region with the highest African ancestry, Amazonia harboured the highest Native ancestry and the Andean and Orinoquían regions showed the highest proportion of European ancestry. The Andean region was further sub-divided into 6 sub-regions: North East, Central West, Central East, West, South West and South East. Among these regions, the South West region showed a significantly lower European admixture than the other regions. Hardy-Weinberg equilibrium and variance values of ancestry among individuals within populations showed a potential stratification of the Pacific population. PMID:27736937

  4. Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

    PubMed Central

    Browning, Sharon R.; Grinde, Kelsey; Plantinga, Anna; Gogarten, Stephanie M.; Stilp, Adrienne M.; Kaplan, Robert C.; Avilés-Santa, M. Larissa; Browning, Brian L.; Laurie, Cathy C.

    2016-01-01

    We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease. PMID:27172203

  5. Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    PubMed

    Browning, Sharon R; Grinde, Kelsey; Plantinga, Anna; Gogarten, Stephanie M; Stilp, Adrienne M; Kaplan, Robert C; Avilés-Santa, M Larissa; Browning, Brian L; Laurie, Cathy C

    2016-06-01

    We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease.

  6. Genome-wide methylation patterns provide insight into differences in breast tumor biology between American women of African and European ancestry.

    PubMed

    Ambrosone, Christine B; Young, Allyson C; Sucheston, Lara E; Wang, Dan; Yan, Li; Liu, Song; Tang, Li; Hu, Qiang; Freudenheim, Jo L; Shields, Peter G; Morrison, Carl D; Demissie, Kitaw; Higgins, Michael J

    2014-01-15

    American women of African ancestry (AA) are more likely than European-Americans (EA) to be diagnosed with aggressive, estrogen receptor (ER) negative breast tumors; mechanisms underlying these disparities are poorly understood. We conducted a genome wide (450K loci) methylation analysis to determine if there were differences in DNA methylation patterns between tumors from AA and EA women and if these differences were similar for both ER positive and ER negative breast cancer. Methylation levels at CpG loci within CpG islands (CGI)s and CGI-shores were significantly higher in tumors (n=138) than in reduction mammoplasty samples (n=124). In hierarchical cluster analysis, there was separation between tumor and normal samples, and in tumors, there was delineation by ER status, but not by ancestry. However, differential methylation analysis identified 157 CpG loci with a mean β value difference of at least 0.17 between races, with almost twice as many differences in ER-negative tumors compared to ER-positive cancers. This first genome-wide methylation study to address disparities indicates that there are likely differing etiologic pathways for the development of ER negative breast cancer between AA and EA women. Further investigation of the genes most differentially methylated by race in ER negative tumors can guide new approaches for cancer prevention and targeted therapies, and elucidate the biologic basis of breast cancer disparities.

  7. Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

    PubMed

    Spracklen, Cassandra N; Chen, Peng; Kim, Young Jin; Wang, Xu; Cai, Hui; Li, Shengxu; Long, Jirong; Wu, Ying; Wang, Ya Xing; Takeuchi, Fumihiko; Wu, Jer-Yuarn; Jung, Keum-Ji; Hu, Cheng; Akiyama, Koichi; Zhang, Yonghong; Moon, Sanghoon; Johnson, Todd A; Li, Huaixing; Dorajoo, Rajkumar; He, Meian; Cannon, Maren E; Roman, Tamara S; Salfati, Elias; Lin, Keng-Hung; Guo, Xiuqing; Sheu, Wayne H H; Absher, Devin; Adair, Linda S; Assimes, Themistocles L; Aung, Tin; Cai, Qiuyin; Chang, Li-Ching; Chen, Chien-Hsiun; Chien, Li-Hsin; Chuang, Lee-Ming; Chuang, Shu-Chun; Du, Shufa; Fan, Qiao; Fann, Cathy S J; Feranil, Alan B; Friedlander, Yechiel; Gordon-Larsen, Penny; Gu, Dongfeng; Gui, Lixuan; Guo, Zhirong; Heng, Chew-Kiat; Hixson, James; Hou, Xuhong; Hsiung, Chao Agnes; Hu, Yao; Hwang, Mi Yeong; Hwu, Chii-Min; Isono, Masato; Juang, Jyh-Ming Jimmy; Khor, Chiea-Chuen; Kim, Yun Kyoung; Koh, Woon-Puay; Kubo, Michiaki; Lee, I-Te; Lee, Sun-Ju; Lee, Wen-Jane; Liang, Kae-Woei; Lim, Blanche; Lim, Sing-Hui; Liu, Jianjun; Nabika, Toru; Pan, Wen-Harn; Peng, Hao; Quertermous, Thomas; Sabanayagam, Charumathi; Sandow, Kevin; Shi, Jinxiu; Sun, Liang; Tan, Pok Chien; Tan, Shu-Pei; Taylor, Kent D; Teo, Yik-Ying; Toh, Sue-Anne; Tsunoda, Tatsuhiko; van Dam, Rob M; Wang, Aili; Wang, Feijie; Wang, Jie; Wei, Wen Bin; Xiang, Yong-Bing; Yao, Jie; Yuan, Jian-Min; Zhang, Rong; Zhao, Wanting; Chen, Yii-Der Ida; Rich, Stephen S; Rotter, Jerome I; Wang, Tzung-Dau; Wu, Tangchun; Lin, Xu; Han, Bok-Ghee; Tanaka, Toshihiro; Cho, Yoon Shin; Katsuya, Tomohiro; Jia, Weiping; Jee, Sun-Ha; Chen, Yuan-Tsong; Kato, Norihiro; Jonas, Jost B; Cheng, Ching-Yu; Shu, Xiao-Ou; He, Jiang; Zheng, Wei; Wong, Tien-Yin; Huang, Wei; Kim, Bong-Jo; Tai, E-Shyong; Mohlke, Karen L; Sim, Xueling

    2017-02-21

    Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.

  8. Straightforward inference of ancestry and admixture proportions through ancestry-informative insertion deletion multiplexing.

    PubMed

    Pereira, Rui; Phillips, Christopher; Pinto, Nádia; Santos, Carla; dos Santos, Sidney Emanuel Batista; Amorim, António; Carracedo, Ángel; Gusmão, Leonor

    2012-01-01

    Ancestry-informative markers (AIMs) show high allele frequency divergence between different ancestral or geographically distant populations. These genetic markers are especially useful in inferring the likely ancestral origin of an individual or estimating the apportionment of ancestry components in admixed individuals or populations. The study of AIMs is of great interest in clinical genetics research, particularly to detect and correct for population substructure effects in case-control association studies, but also in population and forensic genetics studies. This work presents a set of 46 ancestry-informative insertion deletion polymorphisms selected to efficiently measure population admixture proportions of four different origins (African, European, East Asian and Native American). All markers are analyzed in short fragments (under 230 basepairs) through a single PCR followed by capillary electrophoresis (CE) allowing a very simple one tube PCR-to-CE approach. HGDP-CEPH diversity panel samples from the four groups, together with Oceanians, were genotyped to evaluate the efficiency of the assay in clustering populations from different continental origins and to establish reference databases. In addition, other populations from diverse geographic origins were tested using the HGDP-CEPH samples as reference data. The results revealed that the AIM-INDEL set developed is highly efficient at inferring the ancestry of individuals and provides good estimates of ancestry proportions at the population level. In conclusion, we have optimized the multiplexed genotyping of 46 AIM-INDELs in a simple and informative assay, enabling a more straightforward alternative to the commonly available AIM-SNP typing methods dependent on complex, multi-step protocols or implementation of large-scale genotyping technologies.

  9. Correlation of E-selectin concentrations with carotid intima-media thickness and cardio-metabolic profile of mixed ancestry South Africans: a cross-sectional study.

    PubMed

    Zemlin, Annalise E; Matsha, Tandi E; Kengne, Andre P; Hon, Gloudina M; Erasmus, Rajiv T

    2017-01-01

    Background E-selectin, an adhesion molecule, is a specific marker of endothelial dysfunction. High concentrations have been reported in type 2 diabetes and disorders with high risk of cardiovascular disease (CVD). Measurement of carotid intima-media thickness (CIMT) is a surrogate marker of early atherosclerosis. We examined the relationship between E-selectin concentrations, CIMT and cardio-metabolic traits in normo- and hyperglycaemic mixed ancestry South Africans. Methods E-selectin concentrations were determined in 308 subjects from the Cape Town Bellville South Community-based study on a mixed ancestry population. Their correlation with CIMT and cardio-metabolic profile used robust correlations and linear regression models. Results E-selectin concentrations were significantly higher in the hyperglycaemic (median 139.8 µg/L) compared to the normoglycaemic group (median 118.8 µg/L), ( p = 0.0007). Significant differences between the two groups were found for markers of glycaemia and adiposity, but not for CIMT. Significant correlations were found between E-selectin and age, markers of glycaemia and inflammation, central obesity and lipid variables. Associations remained significant only with age, hyperglycaemia and C-reactive protein in robust linear regression models. In similar regressions models, age and gender were the main predictors of CIMT, which was not associated with E-selectin. Conclusions E-selectin concentrations in this study were associated with hyperglycaemia, possibly reflecting early endothelial damage. However, E-selectin was not useful to assess CIMT, a marker of subclinical atherosclerosis, which appeared to be determined by ageing and male gender.

  10. Genetic Ancestry in Lung-Function Predictions

    PubMed Central

    Kumar, Rajesh; Seibold, Max A.; Aldrich, Melinda C.; Williams, L. Keoki; Reiner, Alex P.; Colangelo, Laura; Galanter, Joshua; Gignoux, Christopher; Hu, Donglei; Sen, Saunak; Choudhry, Shweta; Peterson, Edward L.; Rodriguez-Santana, Jose; Rodriguez-Cintron, William; Nalls, Michael A.; Leak, Tennille S.; O’Meara, Ellen; Meibohm, Bernd; Kritchevsky, Stephen B.; Li, Rongling; Harris, Tamara B.; Nickerson, Deborah A.; Fornage, Myriam; Enright, Paul; Ziv, Elad; Smith, Lewis J.; Liu, Kiang; Burchard, Esteban González

    2010-01-01

    BACKGROUND Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American. METHODS We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations. RESULTS African ancestry was inversely related to forced expiratory volume in 1 second (FEV1) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV1) in 4 to 5% of participants. CONCLUSIONS Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity. (Funded by the National

  11. Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry.

    PubMed

    Qian, Frank; Feng, Ye; Zheng, Yonglan; Ogundiran, Temidayo O; Ojengbede, Oladosu; Zheng, Wei; Blot, William; Ambrosone, Christine B; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah; Bandera, Elisa V; Ingles, Sue A; Press, Michael F; Nathanson, Katherine L; Hennis, Anselm; Nemesure, Barbara; Ambs, Stefan; Kolonel, Laurence N; Olopade, Olufunmilayo I; Haiman, Christopher A; Huo, Dezheng

    2016-10-01

    MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.

  12. A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set.

    PubMed

    Santos, Hadassa C; Horimoto, Andréa V R; Tarazona-Santos, Eduardo; Rodrigues-Soares, Fernanda; Barreto, Mauricio L; Horta, Bernardo L; Lima-Costa, Maria F; Gouveia, Mateus H; Machado, Moara; Silva, Thiago M; Sanches, José M; Esteban, Nubia; Magalhaes, Wagner C S; Rodrigues, Maíra R; Kehdy, Fernanda S G; Pereira, Alexandre C

    2016-05-01

    The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals.

  13. Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.

    PubMed

    Bhatia, Gaurav; Patterson, Nick; Pasaniuc, Bogdan; Zaitlen, Noah; Genovese, Giulio; Pollack, Samuela; Mallick, Swapan; Myers, Simon; Tandon, Arti; Spencer, Chris; Palmer, Cameron D; Adeyemo, Adebowale A; Akylbekova, Ermeg L; Cupples, L Adrienne; Divers, Jasmin; Fornage, Myriam; Kao, W H Linda; Lange, Leslie; Li, Mingyao; Musani, Solomon; Mychaleckyj, Josyf C; Ogunniyi, Adesola; Papanicolaou, George; Rotimi, Charles N; Rotter, Jerome I; Ruczinski, Ingo; Salako, Babatunde; Siscovick, David S; Tayo, Bamidele O; Yang, Qiong; McCarroll, Steve; Sabeti, Pardis; Lettre, Guillaume; De Jager, Phil; Hirschhorn, Joel; Zhu, Xiaofeng; Cooper, Richard; Reich, David; Wilson, James G; Price, Alkes L

    2011-09-09

    The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (F(ST) < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10(-11)) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers.

  14. Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations.

    PubMed

    Hernandez-Suarez, Gustavo; Sanabria, Maria Carolina; Serrano, Marta; Herran, Oscar F; Perez, Jesus; Plata, Jose L; Zabaleta, Jovanny; Tenesa, Albert

    2014-10-01

    Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11-0.15) and cancer cases (0.14, 95% CI=0.12-0.16) compared with controls (0.11, 95% CI=0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97-1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population.

  15. Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

    PubMed Central

    2012-01-01

    Background A recent meta-analysis described a variant (p.Ile2984Val) in the cubilin gene (CUBN) that is associated with levels of albuminuria in the general population and in diabetics. Methods We implemented a Linkage Disequilibrium (LD) search with data from the 1000 Genomes Project, on African and European population genomic sequences. Results We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs) in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly), and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans. Conclusions Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus. PMID:23114252

  16. β-T594M epithelial sodium channel gene polymorphism and essential hypertension in individuals of Indo-Aryan ancestry in Northern India

    PubMed Central

    Gupta, Mohit D.; Girish, M.P.; Sikdar, Sunandan; Ahuja, Ramandeep; Shah, Dhaval; Kumar, Rahul; Rain, Manjari; Nejatizadeh, Azim; Tyagi, Sanjay; Pasha, Qadar

    2014-01-01

    Background The T594M variant of the β-subunit of the sodium epithelial channel (ENaC) gene may contribute to hypertension in individuals of Indo-Aryan origin. Methods Present study was performed to assess the role of the ENaC gene variant as an independent risk factor for hypertension in subjects of Indo-Aryan ancestry. A total of 150 patients of recently detected essential hypertension and 150 matched controls were genotyped for the T594M polymorphism of the ENaC gene by PCR–RFLP method. Results β-T594M mutation was found to be non-polymorphic. There was major genotype call in both the groups i.e. cases and controls. Other phenotypic parameters like age, sex and body mass index were also similar among hypertensive patients and controls (P > 0.05). Hypertensive patients had significantly higher total cholesterol and triglycerides compared with controls (P < 0.0001). Conclusion These results do not suggest an important role for the T594M variant of the ENaC gene contributing to either the development or severity of hypertension in subjects of Indo-Aryan ancestry. PMID:25173196

  17. Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

    PubMed Central

    Reinier, Kyndaron; Teodorescu, Carmen; Uy-Evanado, Audrey; Carter-Monroe, Naima; Kaikkonen, Kari S.; Kortelainen, Marja-Leena; Boucher, Gabrielle; Lagacé, Caroline; Moes, Anna; Zhao, XiaoQing; Kolodgie, Frank; Rivadeneira, Fernando; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, André G.; Marsman, Roos F.; Pazoki, Raha; Bardai, Abdennasser; Koster, Rudolph W.; Dehghan, Abbas; Hwang, Shih-Jen; Bhatnagar, Pallav; Post, Wendy; Hilton, Gina; Prineas, Ronald J.; Li, Man; Köttgen, Anna; Ehret, Georg; Boerwinkle, Eric; Coresh, Josef; Kao, W. H. Linda; Psaty, Bruce M.; Tomaselli, Gordon F.; Sotoodehnia, Nona; Siscovick, David S.; Burke, Greg L.; Marbán, Eduardo; Spooner, Peter M.; Cupples, L. Adrienne; Jui, Jonathan; Gunson, Karen; Kesäniemi, Y. Antero; Wilde, Arthur A. M.; Tardif, Jean-Claude; O'Donnell, Christopher J.; Bezzina, Connie R.; Virmani, Renu; Stricker, Bruno H. C. h.; Tan, Hanno L.; Albert, Christine M.; Chakravarti, Aravinda; Rioux, John D.; Huikuri, Heikki V.; Chugh, Sumeet S.

    2011-01-01

    Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). PMID:21738491

  18. Ancestry Dependent DNA Methylation and Influence of Maternal Nutrition

    PubMed Central

    Mozhui, Khyobeni; Smith, Alicia K.; Tylavsky, Frances A.

    2015-01-01

    There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112) and European American (EA; N = 91) participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition—specifically, plasma levels of vitamin D and folate during pregnancy—on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC). Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome. PMID:25742137

  19. Frequency of TNFA, INFG, and IL10 Gene Polymorphisms and Their Association with Malaria Vivax and Genomic Ancestry

    PubMed Central

    dos Santos, Sidney Emanuel Batista

    2016-01-01

    Polymorphisms in cytokine genes can alter the production of these proteins and consequently affect the immune response. The trihybrid heterogeneity of the Brazilian population is characterized as a condition for the use of ancestry informative markers. The objective of this study was to evaluate the frequency of -1031T>C, -308G>A and -238G>A TNFA, +874 A>T IFNG and -819C>T, and -592C>A IL10 gene polymorphisms and their association with malaria vivax and genomic ancestry. Samples from 90 vivax malaria-infected individuals and 51 noninfected individuals from northern Brazil were evaluated. Genotyping was carried out by using ASO-PCR or PCR/RFLP. The genomic ancestry of the individuals was classified using 48 insertion/deletion polymorphism biallelic markers. There were no differences in the proportions of African, European, and Native American ancestry between men and women. No significant association was observed for the allele and genotype frequencies of the 6 SNPs between malaria-infected and noninfected individuals. However, there was a trend toward decreasing the frequency of individuals carrying the TNF-308A allele with the increasing proportion of European ancestry. No ethnic-specific SNPs were identified, and there was no allelic or genotype association with susceptibility or resistance to vivax malaria. Understanding the genomic mechanisms by which ancestry influences this association is critical and requires further study. PMID:27999453

  20. Denisovan Ancestry in East Eurasian and Native American Populations.

    PubMed

    Qin, Pengfei; Stoneking, Mark

    2015-10-01

    Although initial studies suggested that Denisovan ancestry was found only in modern human populations from island Southeast Asia and Oceania, more recent studies have suggested that Denisovan ancestry may be more widespread. However, the geographic extent of Denisovan ancestry has not been determined, and moreover the relationship between the Denisovan ancestry in Oceania and that elsewhere has not been studied. Here we analyze genome-wide single nucleotide polymorphism data from 2,493 individuals from 221 worldwide populations, and show that there is a widespread signal of a very low level of Denisovan ancestry across Eastern Eurasian and Native American (EE/NA) populations. We also verify a higher level of Denisovan ancestry in Oceania than that in EE/NA; the Denisovan ancestry in Oceania is correlated with the amount of New Guinea ancestry, but not the amount of Australian ancestry, indicating that recent gene flow from New Guinea likely accounts for signals of Denisovan ancestry across Oceania. However, Denisovan ancestry in EE/NA populations is equally correlated with their New Guinea or their Australian ancestry, suggesting a common source for the Denisovan ancestry in EE/NA and Oceanian populations. Our results suggest that Denisovan ancestry in EE/NA is derived either from common ancestry with, or gene flow from, the common ancestor of New Guineans and Australians, indicating a more complex history involving East Eurasians and Oceanians than previously suspected.

  1. Ancestry analysis reveals a predominant Native American component with moderate European admixture in Bolivians.

    PubMed

    Heinz, Tanja; Alvarez-Iglesias, Vanesa; Pardo-Seco, Jacobo; Taboada-Echalar, Patricia; Gómez-Carballa, Alberto; Torres-Balanza, Antonio; Rocabado, Omar; Carracedo, Angel; Vullo, Carlos; Salas, Antonio

    2013-09-01

    We have genotyped 46 Ancestry Informative Markers (AIMs) in two of the most populated areas in Bolivia, namely, La Paz (Andean region; n=105), and Chuquisaca (Sub-Andean region; n=73). Using different analytical tools, we inferred admixture proportions of these two American communities by comparing the genetic profiles with those publicly available from the CEPH (Centre d'Etude du Polymorphisme Humain) panel representing three main continental groups (Africa, Europe, and America). By way of simulations, we first evaluated the minimum sample size needed in order to obtain accurate estimates of ancestry proportions. The results indicated that sample sizes above 30 individuals could be large enough to estimate main continental ancestry proportions using the 46 AIMs panel. With the exception of a few individuals, the results also indicated that Bolivians showed a predominantly Native American ancestry with variable levels of European admixture. The proportions of ancestry were statistically different in La Paz and Chuquisaca: the Native American component was 86% and 77% (Mann-Whitney U-test: un-adjusted P-value=2.1×10(-5)), while the European ancestry was 13% and 21% (Mann-Whitney U-test: un-adjusted P-value=3.6×10(-5)), respectively. The African ancestry in Bolivians captured by the AIMs analyzed in the present study was below 2%. The inferred ancestry of Bolivians fits well with previous studies undertaken on haplotype data, indicating a major proportion of Native American lineages. The genetic differences observed in these two groups suggest that forensic genetic analysis should be better performed based on local databases built in the main Bolivian areas.

  2. Male ancestry structure and interethnic admixture in African-descent communities from the Amazon as revealed by Y-chromosome Strs.

    PubMed

    Palha, Teresinha de Jesus Brabo Ferreira; Ribeiro-Rodrigues, Elzemar Martins; Ribeiro-dos-Santos, Andrea; Guerreiro, João Farias; de Moura, Luciene Soraya Souza; Santos, Sidney

    2011-03-01

    Some genetic markers on both the Y chromosome and mtDNA are highly polymorphic and population-specific in humans, representing useful tools for reconstructing the past history of populations with poor historical records. Such lack of information is usually true in the case of recent African-descent populations of the New World founded by fugitive slaves throughout the slavery period in the Americas, particularly in Brazil, where those communities are known as quilombos. Aiming to recover male-derived ethnic structure of nine quilombos from the Brazilian Amazon, a total of 300 individuals, belonging to Mazagão Velho (N = 24), Curiaú (N = 48), Mazagão (N = 36), Trombetas (N = 20), Itacoã (N = 22), Saracura (N = 46), Marajó (N = 58), Pitimandeua (N = 26), and Pontal (N = 20), were investigated for nine Y-STRs (DYS393, DYS19, DYS390, DYS389 I, DYS389 II, DYS392, DYS391, DYS385 I/II). From the 169 distinct haplotypes obtained, 120 were singletons. The results suggest the West African coast as the main origin of slaves brought to Brazil (54% of male contribution); the European contribution was high (41%), while the Amerindian's was low (5%). Those results contrast with previous mtDNA data that showed high Amerindian female contribution (46.6%) in African-descent populations. AMOVA suggests that the genetic differentiation among the quilombos is mainly influenced by admixture with European. However, when restricting AMOVA to African-specific haplotypes, low differentiation was detected, suggesting great genetic homogeneity of the African founding populations and/or a later homogenization by intense slave trade inside Brazil.

  3. Evaluating self-declared ancestry of U.S. Americans with autosomal, Y-chromosomal and mitochondrial DNA.

    PubMed

    Lao, Oscar; Vallone, Peter M; Coble, Michael D; Diegoli, Toni M; van Oven, Mannis; van der Gaag, Kristiaan J; Pijpe, Jeroen; de Knijff, Peter; Kayser, Manfred

    2010-12-01

    The current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited DNA markers sensitive for indicating continental genetic ancestry in all four major U.S. American groups. We found that self-declared U.S. Hispanics and U.S. African Americans tend to show variable degrees of continental genetic admixture among the three genetic systems, with evidence for a marked sex-biased admixture history. Moreover, for these two groups we observed significant regional variation across the country in genetic admixture. In contrast, self-declared U.S. European and U.S. Asian Americans were genetically more homogeneous at the continental ancestry level. Two autosomal ancestry-sensitive markers located in skin pigmentation candidate genes showed significant differences in self-declared U.S. African Americans or U.S. European Americans, relative to their assumed parental populations from Africa or Europe. This provides genetic support for the importance of skin color in the complex process of ancestry identification.

  4. Evaluating Self-declared Ancestry of U.S. Americans with Autosomal, Y-chromosomal and Mitochondrial DNA

    PubMed Central

    Lao, Oscar; Vallone, Peter M; Coble, Michael D; Diegoli, Toni M; van Oven, Mannis; van der Gaag, Kristiaan J; Pijpe, Jeroen; de Knijff, Peter; Kayser, Manfred

    2010-01-01

    The current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited DNA markers sensitive for indicating continental genetic ancestry in all four major U.S. American groups. We found that self-declared U.S. Hispanics and U.S. African Americans tend to show variable degrees of continental genetic admixture among the three genetic systems, with evidence for a marked sex-biased admixture history. Moreover, for these two groups we observed significant regional variation across the country in genetic admixture. In contrast, self-declared U.S. European and U.S. Asian Americans were genetically more homogeneous at the continental ancestry level. Two autosomal ancestry-sensitive markers located in skin pigmentation candidate genes showed significant differences in self-declared U.S. African Americans or U.S. European Americans, relative to their assumed parental populations from Africa or Europe. This provides genetic support for the importance of skin color in the complex process of ancestry identification. © 2010 Wiley-Liss, Inc. PMID:20886636

  5. STRATEGIES FOR EQUITABLE PHARMACOGENOMIC-GUIDED WARFARIN DOSING AMONG EUROPEAN AND AFRICAN AMERICAN INDIVIDUALS IN A CLINICAL POPULATION

    PubMed Central

    WILEY, LAURA K.; VANHOUTEN, JACOB P.; SAMUELS, DAVID C.; ALDRICH, MELINDA C.; RODEN, DAN M.; PETERSON, JOSH F.; DENNY, JOSHUA C.

    2017-01-01

    The blood thinner warfarin has a narrow therapeutic range and high inter- and intra-patient variability in therapeutic doses. Several studies have shown that pharmacogenomic variants help predict stable warfarin dosing. However, retrospective and randomized controlled trials that employ dosing algorithms incorporating pharmacogenomic variants under perform in African Americans. This study sought to determine if: 1) including additional variants associated with warfarin dose in African Americans, 2) predicting within single ancestry groups rather than a combined population, or 3) using percentage African ancestry rather than observed race, would improve warfarin dosing algorithms in African Americans. Using BioVU, the Vanderbilt University Medical Center biobank linked to electronic medical records, we compared 25 modeling strategies to existing algorithms using a cohort of 2,181 warfarin users (1,928 whites, 253 blacks). We found that approaches incorporating additional variants increased model accuracy, but not in clinically significant ways. Race stratification increased model fidelity for African Americans, but the improvement was small and not likely to be clinically significant. Use of percent African ancestry improved model fit in the context of race misclassification. PMID:27897005

  6. Genomic Insights into the Ancestry and Demographic History of South America.

    PubMed

    Homburger, Julian R; Moreno-Estrada, Andrés; Gignoux, Christopher R; Nelson, Dominic; Sanchez, Elena; Ortiz-Tello, Patricia; Pons-Estel, Bernardo A; Acevedo-Vasquez, Eduardo; Miranda, Pedro; Langefeld, Carl D; Gravel, Simon; Alarcón-Riquelme, Marta E; Bustamante, Carlos D

    2015-12-01

    South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9-14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical

  7. Genomic Insights into the Ancestry and Demographic History of South America

    PubMed Central

    Homburger, Julian R.; Moreno-Estrada, Andrés; Gignoux, Christopher R.; Nelson, Dominic; Sanchez, Elena; Ortiz-Tello, Patricia; Pons-Estel, Bernardo A.; Acevedo-Vasquez, Eduardo; Miranda, Pedro; Langefeld, Carl D.; Gravel, Simon; Alarcón-Riquelme, Marta E.; Bustamante, Carlos D.

    2015-01-01

    South America has a complex demographic history shaped by multiple migration and admixture events in pre- and post-colonial times. Settled over 14,000 years ago by Native Americans, South America has experienced migrations of European and African individuals, similar to other regions in the Americas. However, the timing and magnitude of these events resulted in markedly different patterns of admixture throughout Latin America. We use genome-wide SNP data for 437 admixed individuals from 5 countries (Colombia, Ecuador, Peru, Chile, and Argentina) to explore the population structure and demographic history of South American Latinos. We combined these data with population reference panels from Africa, Asia, Europe and the Americas to perform global ancestry analysis and infer the subcontinental origin of the European and Native American ancestry components of the admixed individuals. By applying ancestry-specific PCA analyses we find that most of the European ancestry in South American Latinos is from the Iberian Peninsula; however, many individuals trace their ancestry back to Italy, especially within Argentina. We find a strong gradient in the Native American ancestry component of South American Latinos associated with country of origin and the geography of local indigenous populations. For example, Native American genomic segments in Peruvians show greater affinities with Andean indigenous peoples like Quechua and Aymara, whereas Native American haplotypes from Colombians tend to cluster with Amazonian and coastal tribes from northern South America. Using ancestry tract length analysis we modeled post-colonial South American migration history as the youngest in Latin America during European colonization (9–14 generations ago), with an additional strong pulse of European migration occurring between 3 and 9 generations ago. These genetic footprints can impact our understanding of population-level differences in biomedical traits and, thus, inform future medical

  8. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry

    PubMed Central

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M

    2015-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case–control study of men 40–80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00–1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01–1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04–4.43 and OR, 2.47 CI, 1.20–4.90 for tertile 3 (Ptrend = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. PMID:25858172

  9. Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

    PubMed Central

    Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P

    2015-01-01

    from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups. CONCLUSION: There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort. PMID:26052389

  10. What Is Genetic Ancestry Testing?

    MedlinePlus

    ... Testing What is genetic ancestry testing? What is genetic ancestry testing? Genetic ancestry testing, or genetic genealogy, ... mixed with other groups. For more information about genetic ancestry testing: The University of Utah provides video ...

  11. Socioeconomic and Nutritional Factors Account for the Association of Gastric Cancer with Amerindian Ancestry in a Latin American Admixed Population

    PubMed Central

    Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Herrera, Phabiola; Cabrera, Lilia; Hooper, Catherine C.; Cok, Jaime; Combe, Juan M.; Vargas, Gloria; Prado, William A.; Schneider, Silvana; Kehdy, Fernanda; Rodrigues, Maira R.; Chanock, Stephen J.; Berg, Douglas E.; Gilman, Robert H.; Tarazona-Santos, Eduardo

    2012-01-01

    Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group. PMID:22870209

  12. Socioeconomic and nutritional factors account for the association of gastric cancer with Amerindian ancestry in a Latin American admixed population.

    PubMed

    Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Herrera, Phabiola; Cabrera, Lilia; Hooper, Catherine C; Cok, Jaime; Combe, Juan M; Vargas, Gloria; Prado, William A; Schneider, Silvana; Kehdy, Fernanda; Rodrigues, Maira R; Chanock, Stephen J; Berg, Douglas E; Gilman, Robert H; Tarazona-Santos, Eduardo

    2012-01-01

    Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.

  13. Horizontal and vertical dimensions of individualism-collectivism: a comparison of African Americans and European Americans.

    PubMed

    Komarraju, Meera; Cokley, Kevin O

    2008-10-01

    The current study examined ethnic differences in horizontal and vertical dimensions of individualism and collectivism among 96 African American and 149 European American college students. Participants completed the 32-item Singelis et al. (1995) Individualism/Collectivism Scale. Multivariate analyses of variance results yielded a main effect for ethnicity, with African Americans being significantly higher on horizontal individualism and European Americans being higher on horizontal collectivism and vertical individualism. A moderated multiple regression analysis indicated that ethnicity significantly moderated the relationship between individualism and collectivism. Individualism and collectivism were significantly and positively associated among African Americans, but not associated among European Americans. In addition, collectivism was related to grade point average for African Americans but not for European Americans. Contrary to the prevailing view of individualism-collectivism being unipolar, orthogonal dimensions, results provide support for individualism-collectivism to be considered as unipolar, related dimensions for African Americans.

  14. Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages

    PubMed Central

    Palopoli, Michael F.; Fergus, Daniel J.; Minot, Samuel; Pei, Dorothy T.; Simison, W. Brian; Fernandez-Silva, Iria; Thoemmes, Megan S.; Dunn, Robert R.; Trautwein, Michelle

    2015-01-01

    Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement. PMID:26668374

  15. Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages.

    PubMed

    Palopoli, Michael F; Fergus, Daniel J; Minot, Samuel; Pei, Dorothy T; Simison, W Brian; Fernandez-Silva, Iria; Thoemmes, Megan S; Dunn, Robert R; Trautwein, Michelle

    2015-12-29

    Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement.

  16. No evidence for a large difference in ALS frequency in populations of African and European origin: a population based study in inner city London.

    PubMed

    Rojas-Garcia, Ricardo; Scott, Kirsten M; Roche, Jose Carlos; Scotton, William; Martin, Naomi; Janssen, Anna; Goldstein, Laura H; Leigh, P Nigel; Ellis, Cathy M; Shaw, Christopher E; Al-Chalabi, Ammar

    2012-01-01

    Abstract Previous studies have suggested a lower incidence of ALS in people of African origin. We used a population based register in an urban setting from inner city London postcodes where there is a large population of people of African ancestry to compare the frequency of ALS in people of European and African origin. Population statistics stratified by age, gender and ethnicity were obtained from the 2001 census. Incidence and prevalence were calculated in each ethnic group. Results showed that in a population of 683,194, of which 22% were of African ancestry, 88 individuals with ALS were identified over a seven-year period, including 14 people with African ancestry. The adjusted incidence in people of African ancestry was 1.35 per 100,000 person-years (95% CI 0.72-2.3) and in those of European ancestry 1.97 per 100,000 person-years (95% CI 1.55-2.48). In conclusion, in this small population based study we could not detect a difference in rates of ALS between people of African ancestry and those of European ancestry.

  17. A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome.

    PubMed

    Mathias, Rasika Ann; Taub, Margaret A; Gignoux, Christopher R; Fu, Wenqing; Musharoff, Shaila; O'Connor, Timothy D; Vergara, Candelaria; Torgerson, Dara G; Pino-Yanes, Maria; Shringarpure, Suyash S; Huang, Lili; Rafaels, Nicholas; Boorgula, Meher Preethi; Johnston, Henry Richard; Ortega, Victor E; Levin, Albert M; Song, Wei; Torres, Raul; Padhukasahasram, Badri; Eng, Celeste; Mejia-Mejia, Delmy-Aracely; Ferguson, Trevor; Qin, Zhaohui S; Scott, Alan F; Yazdanbakhsh, Maria; Wilson, James G; Marrugo, Javier; Lange, Leslie A; Kumar, Rajesh; Avila, Pedro C; Williams, L Keoki; Watson, Harold; Ware, Lorraine B; Olopade, Christopher; Olopade, Olufunmilayo; Oliveira, Ricardo; Ober, Carole; Nicolae, Dan L; Meyers, Deborah; Mayorga, Alvaro; Knight-Madden, Jennifer; Hartert, Tina; Hansel, Nadia N; Foreman, Marilyn G; Ford, Jean G; Faruque, Mezbah U; Dunston, Georgia M; Caraballo, Luis; Burchard, Esteban G; Bleecker, Eugene; Araujo, Maria Ilma; Herrera-Paz, Edwin Francisco; Gietzen, Kimberly; Grus, Wendy E; Bamshad, Michael; Bustamante, Carlos D; Kenny, Eimear E; Hernandez, Ryan D; Beaty, Terri H; Ruczinski, Ingo; Akey, Joshua; Barnes, Kathleen C

    2016-10-11

    The African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow across multiple regions. Moreover, we refine estimates on the burden of deleterious variants carried across populations and how this varies with African ancestry. Our data are an important resource for empowering disease mapping studies in African-admixed individuals and will facilitate gene discovery for diseases disproportionately affecting individuals of African ancestry.

  18. A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome

    PubMed Central

    Mathias, Rasika Ann; Taub, Margaret A.; Gignoux, Christopher R.; Fu, Wenqing; Musharoff, Shaila; O'Connor, Timothy D.; Vergara, Candelaria; Torgerson, Dara G.; Pino-Yanes, Maria; Shringarpure, Suyash S.; Huang, Lili; Rafaels, Nicholas; Boorgula, Meher Preethi; Johnston, Henry Richard; Ortega, Victor E.; Levin, Albert M.; Song, Wei; Torres, Raul; Padhukasahasram, Badri; Eng, Celeste; Mejia-Mejia, Delmy-Aracely; Ferguson, Trevor; Qin, Zhaohui S.; Scott, Alan F.; Yazdanbakhsh, Maria; Wilson, James G.; Marrugo, Javier; Lange, Leslie A.; Kumar, Rajesh; Avila, Pedro C.; Williams, L. Keoki; Watson, Harold; Ware, Lorraine B.; Olopade, Christopher; Olopade, Olufunmilayo; Oliveira, Ricardo; Ober, Carole; Nicolae, Dan L.; Meyers, Deborah; Mayorga, Alvaro; Knight-Madden, Jennifer; Hartert, Tina; Hansel, Nadia N.; Foreman, Marilyn G.; Ford, Jean G.; Faruque, Mezbah U.; Dunston, Georgia M.; Caraballo, Luis; Burchard, Esteban G.; Bleecker, Eugene; Araujo, Maria Ilma; Herrera-Paz, Edwin Francisco; Gietzen, Kimberly; Grus, Wendy E.; Bamshad, Michael; Bustamante, Carlos D.; Kenny, Eimear E.; Hernandez, Ryan D.; Beaty, Terri H.; Ruczinski, Ingo; Akey, Joshua; Campbell, Monica; Chavan, Sameer; Foster, Cassandra; Gao, Li; Horowitz, Edward; Ortiz, Romina; Potee, Joseph; Gao, Jingjing; Hu, Yijuan; Hansen, Mark; Deshpande, Aniket; Locke, Devin P.; Grammer, Leslie; Kim, Kwang-YounA; Schleimer, Robert; De La Vega, Francisco M.; Szpiech, Zachary A.; Oluwole, Oluwafemi; Arinola, Ganiyu; Correa, Adolfo; Musani, Solomon; Chong, Jessica; Nickerson, Deborah; Reiner, Alexander; Maul, Pissamai; Maul, Trevor; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Luis F.; Ramos, Hector; Saenz, Allan; Varela, Gloria; Vasquez, Olga Marina; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Barnes, Kathleen C.

    2016-01-01

    The African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow across multiple regions. Moreover, we refine estimates on the burden of deleterious variants carried across populations and how this varies with African ancestry. Our data are an important resource for empowering disease mapping studies in African-admixed individuals and will facilitate gene discovery for diseases disproportionately affecting individuals of African ancestry. PMID:27725671

  19. Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine.

    PubMed

    Yang, Nan; Li, Hongzhe; Criswell, Lindsey A; Gregersen, Peter K; Alarcon-Riquelme, Marta E; Kittles, Rick; Shigeta, Russell; Silva, Gabriel; Patel, Pragna I; Belmont, John W; Seldin, Michael F

    2005-12-01

    We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry. Additional analyses showed that, for the majority of samples, the predicted ethnic identity corresponded with the self-identified ethnicity at high probability (P > 0.99). Overall, the study demonstrates that AIMs can provide a useful adjunct to forensic medicine, pharmacogenomics and disease studies in which major ancestry or ethnic affiliation might be linked to specific outcomes.

  20. Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas.

    PubMed

    Galanter, Joshua Mark; Fernandez-Lopez, Juan Carlos; Gignoux, Christopher R; Barnholtz-Sloan, Jill; Fernandez-Rozadilla, Ceres; Via, Marc; Hidalgo-Miranda, Alfredo; Contreras, Alejandra V; Figueroa, Laura Uribe; Raska, Paola; Jimenez-Sanchez, Gerardo; Zolezzi, Irma Silva; Torres, Maria; Ponte, Clara Ruiz; Ruiz, Yarimar; Salas, Antonio; Nguyen, Elizabeth; Eng, Celeste; Borjas, Lisbeth; Zabala, William; Barreto, Guillermo; González, Fernando Rondón; Ibarra, Adriana; Taboada, Patricia; Porras, Liliana; Moreno, Fabián; Bigham, Abigail; Gutierrez, Gerardo; Brutsaert, Tom; León-Velarde, Fabiola; Moore, Lorna G; Vargas, Enrique; Cruz, Miguel; Escobedo, Jorge; Rodriguez-Santana, José; Rodriguez-Cintrón, William; Chapela, Rocio; Ford, Jean G; Bustamante, Carlos; Seminara, Daniela; Shriver, Mark; Ziv, Elad; Burchard, Esteban Gonzalez; Haile, Robert; Parra, Esteban; Carracedo, Angel

    2012-01-01

    Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.

  1. Building a forensic ancestry panel from the ground up: The EUROFORGEN Global AIM-SNP set.

    PubMed

    Phillips, C; Parson, W; Lundsberg, B; Santos, C; Freire-Aradas, A; Torres, M; Eduardoff, M; Børsting, C; Johansen, P; Fondevila, M; Morling, N; Schneider, P; Carracedo, A; Lareu, M V

    2014-07-01

    Emerging next-generation sequencing technologies will enable DNA analyses to add pigmentation predictive and ancestry informative (AIM) SNPs to the range of markers detectable from a single PCR test. This prompted us to re-appraise current forensic and genomics AIM-SNPs and from the best sets, to identify the most divergent markers for a five population group differentiation of Africans, Europeans, East Asians, Native Americans and Oceanians by using our own online genome variation browsers. We prioritized careful balancing of population differentiation across the five group comparisons in order to minimize bias when estimating co-ancestry proportions in individuals with admixed ancestries. The differentiation of European from Middle East or South Asian ancestries was not chosen as a characteristic in order to concentrate on introducing Oceanian differentiation for the first time in a forensic AIM set. We describe a complete set of 128 AIM-SNPs that have near identical population-specific divergence across five continentally defined population groups. The full set can be systematically reduced in size, while preserving the most informative markers and the balance of population-specific divergence in at least four groups. We describe subsets of 88, 55, 28, 20 and 12 AIMs, enabling both new and existing SNP genotyping technologies to exploit the best markers identified for forensic ancestry analysis.

  2. Examining Individualism, Collectivism, and Self-Differentiation in African American College Women.

    ERIC Educational Resources Information Center

    Gushue, George V.; Constantine, Madonna G.

    2003-01-01

    Examines aspects of individualism, collectivism, and self-differentiation in 123 African American women attending a predominantly White university. Results reveled that aspects of individualism and collectivism were differentially related to self-differentiation in African American college women. Implications of the findings are discussed.…

  3. Results from a prostate cancer admixture mapping study in African-American men.

    PubMed

    Bock, Cathryn Hufford; Schwartz, Ann G; Ruterbusch, Julie J; Levin, Albert M; Neslund-Dudas, Christine; Land, Susan J; Wenzlaff, Angela S; Reich, David; McKeigue, Paul; Chen, Wei; Heath, Elisabeth I; Powell, Isaac J; Kittles, Rick A; Rybicki, Benjamin A

    2009-11-01

    There are considerable racial disparities in prostate cancer risk, with a 60% higher incidence rate among African-American (AA) men compared with European-American (EA) men, and a 2.4-fold higher mortality rate in AA men than in EA men. Recently, studies have implicated several African-ancestry associated prostate cancer susceptibility loci on chromosome 8q24. In the current study, we performed admixture mapping in AA men from two independent case-control studies of prostate cancer to confirm the 8q24 ancestry association and also identify other genomic regions that may harbor prostate cancer susceptibility genes. A total of 482 cases and 261 controls were genotyped for 1,509 ancestry informative markers across the genome. The mean estimated individual admixture proportions were 20% European and 80% African. The most significant observed increase in European ancestry occurred at rs2141360 on chromosome 7q31 in both the case-only (P = 0.0000035) and case-control analyses. The most significant observed increase in African ancestry across the genome occurred at a locus on chromosome 5q35 identified by SNPs rs7729084 (case-only analysis P = 0.002), and rs12474977 (case-control analysis P = 0.004), which are separated by 646 kb and were adjacent to one another on the panel. On chromosome 8, rs4367565 was associated with the greatest excess African ancestry in both the case-only and case-control analyses (case-only and case-control P = 0.02), confirming previously reported African-ancestry associations with chromosome 8q24. In conclusion, we confirmed ancestry associations on 8q24, and identified additional ancestry-associated regions potentially harboring prostate cancer susceptibility loci.

  4. Eurasiaplex: a forensic SNP assay for differentiating European and South Asian ancestries.

    PubMed

    Phillips, C; Freire Aradas, A; Kriegel, A K; Fondevila, M; Bulbul, O; Santos, C; Serrulla Rech, F; Perez Carceles, M D; Carracedo, Á; Schneider, P M; Lareu, M V

    2013-05-01

    We have selected a set of single nucleotide polymorphisms (SNPs) with the specific aim of differentiating European and South Asian ancestries. The SNPs were combined into a 23-plex SNaPshot primer extension assay: Eurasiaplex, designed to complement an existing 34-plex forensic ancestry test with both marker sets occupying well-spaced genomic positions, enabling their combination as single profile submissions to the Bayesian Snipper forensic ancestry inference system. We analyzed the ability of Eurasiaplex plus 34plex SNPs to assign ancestry to a total 1648 profiles from 16 European, 7 Middle East, 13 Central-South Asian and 21 East Asian populations. Ancestry assignment likelihoods were estimated from Snipper using training sets of five-group data (three Eurasian groups, East Asian and African genotypes) and four-group data (Middle East genotypes removed). Five-group differentiations gave assignment success of 91% for NW European populations, 72% for Middle East populations and 39% for Central-South Asian populations, indicating Middle East individuals are not reliably differentiated from either Europeans or Central-South Asians. Four-group differentiations provided markedly improved assignment success rates of 97% for most continental Europeans tested (excluding Turkish and Adygei at the far eastern edge of Europe) and 95% for Central-South Asians, despite applying a probability threshold for the highest likelihood ratio above '100 times more likely'. As part of the assessment of the sensitivity of Eurasiaplex to analyze challenging forensic material we detail Eurasiaplex and 34-plex SNP typing to infer ancestry of a cranium recovered from the sea, achieving 82% SNP genotype completeness. Therefore, Eurasiaplex provides an informative and forensically robust approach to the differentiation of European and South Asian ancestries amongst Eurasian populations.

  5. Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens.

    PubMed

    Nédélec, Yohann; Sanz, Joaquín; Baharian, Golshid; Szpiech, Zachary A; Pacis, Alain; Dumaine, Anne; Grenier, Jean-Christophe; Freiman, Andrew; Sams, Aaron J; Hebert, Steven; Pagé Sabourin, Ariane; Luca, Francesca; Blekhman, Ran; Hernandez, Ryan D; Pique-Regi, Roger; Tung, Jenny; Yotova, Vania; Barreiro, Luis B

    2016-10-20

    Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. A total of 9.3% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth. A large proportion of these differences are under genetic control: for 804 genes, more than 75% of ancestry effects on the immune response can be explained by a single cis- or trans-acting expression quantitative trait locus (eQTL). Finally, we show that genetic effects on the immune response are strongly enriched for recent, population-specific signatures of adaptation. Together, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are key to controlling infection.

  6. Risk factors for fracture in middle- and older-age men of African descent

    PubMed Central

    Sheu, Yahtyng; Cauley, Jane A.; Patrick, Alan L.; Wheeler, Victor W.; Bunker, Clareann H.; Zmuda, Joseph M.

    2013-01-01

    Although fracture rates are lower in individuals of African descent compared to individuals of European ancestry, morbidity and mortality following a fracture may be greater in African ancestry individuals. However, fracture risk and associated clinical risk factors have not been well-defined among African ancestry populations, especially among African ancestry men. We used data collected from the Tobago Bone Health Study to examine potential clinical risk factors for incident fractures including demographic information, anthropometric measurements, medical history, lifestyle factors, bone mineral density (BMD) and hip structural geometry. Among 1,933 Afro-Caribbean men aged ≥40 years at study entry (mean age: 57.2 ± 11.0 years), 65 reported at least one new fracture during 10 years of subsequent follow-up. Younger age, mixed Afro-Caribbean ancestry, prior fracture history, BMD and hip structural geometry were statistically significant risk factors for incident fractures. One Standard deviation change in several skeletal parameters (hip BMD, cross-sectional area, outer diameter, cortical thickness and buckling ratio) were each associated with a 35% to 56% increase in incident fracture risk after adjusting for age. Men with a prior fracture history were 3 times more likely to experience a new fracture during follow-up, and the association remained strong after adjusting for age, mixed Afro-Caribbean ancestry and skeletal parameters (hazard ratios ranged 2.72–2.82). Our findings suggest that except for age, risk factors for fracture in men of African ancestry are similar to established risk factors in Caucasian populations. Prior fracture history is a powerful and independent risk factor for incident fractures among African ancestry men and could easily be incorporated into clinical risk evaluation. PMID:23775783

  7. Ancestry, admixture and fitness in Colombian genomes.

    PubMed

    Rishishwar, Lavanya; Conley, Andrew B; Wigington, Charles H; Wang, Lu; Valderrama-Aguirre, Augusto; Jordan, I King

    2015-07-21

    The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%-96.7%), followed by Native American (average = 18.1%, range = 2.1%-33.3%) and African (average = 7.3%, range = 0.2%-38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment.

  8. Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance

    PubMed Central

    Wilson, Robin Taylor; Roff, Alanna N.; Dai, P. Jenny; Fortugno, Tracey; Douds, Jonathan; Chen, Gang; Grove, Gary L.; Nikiforova, Sheila Ongeri; Barnholtz-Sloan, Jill; Frudakis, Tony; Chinchilli, Vernon M.; Hartman, Terryl J.; Demers, Laurence M.; Shriver, Mark D.; Canfield, Victor A.; Cheng, Keith C.

    2012-01-01

    Background Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (SLC45A2 and SLC24A5). Materials and Methods Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (+/− 2 years) and sex. 176 autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites (25(OH)D3, 25(OH)D2 and 24,25(OH)2D3) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)2D3 was calculated as a percent of the parent metabolite (25(OH)D3). Stepwise and backward selection regression models were used to identify leading covariates. Results Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111Thr homozygotes, individuals with the SLC24A5 111Thr/Ala and 111Ala/Ala genotypes had respectively lower levels of 25(OH)D3 (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)2D3 (4.1 and 5.2 percent lower, p-dominant=0.003), controlling for tanning bed use, vitamin D/fish oil supplement intake, race/ethnicity, and genetic ancestry. Results were similar with melanin index adjustment, and were not confounded by glucocorticoid, oral contraceptive, or statin use. Conclusions The SLC24A5 111Ala allele was associated with lower serum vitamin 25(OH)D3 and lower percent 24,25(OH)2D3, independently from melanin index and West African genetic ancestry. PMID:23525585

  9. Ancestry Analysis in the 11-M Madrid Bomb Attack Investigation

    PubMed Central

    Phillips, Christopher; Prieto, Lourdes; Fondevila, Manuel; Salas, Antonio; Gómez-Tato, Antonio; Álvarez-Dios, José; Alonso, Antonio; Blanco-Verea, Alejandro; Brión, María; Montesino, Marta; Carracedo, Ángel; Lareu, María Victoria

    2009-01-01

    The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR) profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a critical part of the investigation and was instigated to help refine the search for further suspects. Although mitochondrial DNA (mtDNA) and Y-chromosome markers routinely demonstrate informative geographic differentiation, the populations compared in this analysis were known to show a proportion of shared mtDNA and Y haplotypes as a result of recent gene-flow across the western Mediterranean, while any two loci can be unrepresentative of the ancestry of an individual as a whole. We based our principal analysis on a validated 34plex autosomal ancestry-informative-marker single nucleotide polymorphism (AIM-SNP) assay to make an assignment of ancestry for DNA from seven unmatched case samples including a handprint from a bag containing undetonated explosives together with personal items recovered from various locations in Madrid associated with the suspects. To assess marker informativeness before genotyping, we predicted the probable classification success for the 34plex assay with standard error estimators for a naïve Bayesian classifier using Moroccan and Spanish training sets (each n = 48). Once misclassification error was found to be sufficiently low, genotyping yielded seven near-complete profiles (33 of 34 AIM-SNPs) that in four cases gave probabilities providing a clear assignment of ancestry. One of the suspects predicted to be North African by AIM-SNP analysis of DNA from a toothbrush was identified late in the investigation as Algerian in origin. The results

  10. Impact of Two Psychosocial Interventions on White and African American Family Caregivers of Individuals with Dementia

    ERIC Educational Resources Information Center

    Burgio, Louis; Stevens, Alan; Guy; Delois; Roth, David L.; Haley, William E.

    2003-01-01

    Purpose: We developed manual-guided, replicable interventions based on common needs and cultural preferences of White and African American family caregivers (CGs) of individuals with dementia, and we evaluated these interventions after a 6-month follow-up. Design and Methods: We randomly assigned White (n = 70) and African American (n = 48) CGs of…

  11. Pacifiplex: an ancestry-informative SNP panel centred on Australia and the Pacific region.

    PubMed

    Santos, Carla; Phillips, Christopher; Fondevila, Manuel; Daniel, Runa; van Oorschot, Roland A H; Burchard, Esteban G; Schanfield, Moses S; Souto, Luis; Uacyisrael, Jolame; Via, Marc; Carracedo, Ángel; Lareu, Maria V

    2016-01-01

    The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population's currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry

  12. Impact of Genetic Ancestry and Socio-Demographic Status on the Clinical Expression of Systemic Lupus Erythematosus in Amerindian-European Populations

    PubMed Central

    Sánchez, Elena; Rasmussen, Astrid; Riba, Laura; Acevedo, Eduardo; Kelly, Jennifer A.; Langefeld, Carl D.; García-De La Torre, Ignacio; Maradiaga-Ceceña, Marco A.; Cardiel, Mario H.; Esquivel-Valerio, Jorge A.; Rodriguez-Amado, Jacqueline; Moctezuma, José Francisco; Miranda, Pedro; Perandones, Carlos; Castel, Cecilia; Laborde, Hugo A.; Alba, Paula; Musuruana, Jorge; Goecke, Annelise; Anaya, Juan-Manuel; Kaufman, Kenneth M.; Adler, Adam; Brown, Elizabeth E.; Alarcón, Graciela S.; Kimberly, Robert P.; Edberg, Jeffrey C.; Criswell, Lindsey A.; Gilkeson, Gary S.; Niewold, Timothy B.; Martin, Javier; Vyse, Timothy J.; Ramsey-Goldman, Rosalind; Petri, Michelle; Merrill, Joan T.; Reveille, John D.; Tsao, Betty P.; Orozco, Lorena; Baca, Vicente; James, Judith A.; Harley, John B.; Tusié-Luna, Teresa; Pons-Estel, Bernardo A.; Jacob, Chaim O.; Alarcón-Riquelme, Marta E.

    2012-01-01

    Objective Amerindian-Europeans, Asians and African-Americans have an excess morbidity from SLE and higher prevalence of lupus nephritis than Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and socio-demographic characteristics and clinical features in a large cohort of Amerindian-European SLE patients. Methods A total of 2116 SLE patients of Amerindian-European origin and 4001 SLE patients of European descent with clinical data were used in the study. Genotyping of 253 continental ancestry informative markers was performed on the Illumina platform. The STRUCTURE and ADMIXTURE software were used to determine genetic ancestry of each individual. Correlation between ancestry and socio-demographic and clinical data were analyzed using logistic regression. Results The average Amerindian genetic ancestry of 2116 SLE patients was 40.7%. There was an increased risk of having renal involvement (P<0.0001, OR= 3.50 95%CI 2.63-4.63) and an early age of onset with the presence of Amerindian genetic ancestry (P<0.0001). Amerindian ancestry protected against photosensitivity (P<0.0001, OR= 0.58 95%CI 0.44-0.76), oral ulcers (P<0.0001, OR= 0.55 95%CI 0.42-0.72), and serositis (P<0.0001, OR= 0.56 95%CI 0.41-0.75) after adjustment by age, gender and age of onset. However, gender and age of onset had stronger effects on malar rash, discoid rash, arthritis and neurological involvement than genetic ancestry. Conclusion In general, genetic Amerindian ancestry correlates with lower socio-demographic status and increases the risk for developing renal involvement and SLE at an earlier age of onset. PMID:22886787

  13. Complex Ancient Genetic Structure and Cultural Transitions in Southern African Populations.

    PubMed

    Montinaro, Francesco; Busby, George B J; Gonzalez-Santos, Miguel; Oosthuitzen, Ockie; Oosthuitzen, Erika; Anagnostou, Paolo; Destro-Bisol, Giovanni; Pascali, Vincenzo L; Capelli, Cristian

    2017-01-01

    The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries.

  14. Genome-wide genotype and sequence-based reconstruction of the 140,000 year history of modern human ancestry

    PubMed Central

    Shriner, Daniel; Tekola-Ayele, Fasil; Adeyemo, Adebowale; Rotimi, Charles N.

    2014-01-01

    We investigated ancestry of 3,528 modern humans from 163 samples. We identified 19 ancestral components, with 94.4% of individuals showing mixed ancestry. After using whole genome sequences to correct for ascertainment biases in genome-wide genotype data, we dated the oldest divergence event to 140,000 years ago. We detected an Out-of-Africa migration 100,000–87,000 years ago, leading to peoples of the Americas, east and north Asia, and Oceania, followed by another migration 61,000–44,000 years ago, leading to peoples of the Caucasus, Europe, the Middle East, and south Asia. We dated eight divergence events to 33,000–20,000 years ago, coincident with the Last Glacial Maximum. We refined understanding of the ancestry of several ethno-linguistic groups, including African Americans, Ethiopians, the Kalash, Latin Americans, Mozabites, Pygmies, and Uygurs, as well as the CEU sample. Ubiquity of mixed ancestry emphasizes the importance of accounting for ancestry in history, forensics, and health. PMID:25116736

  15. Comparing genetic ancestry and self-reported race/ethnicity in a multiethnic population in New York City.

    PubMed

    Lee, Yin Leng; Teitelbaum, Susan; Wolff, Mary S; Wetmur, James G; Chen, Jia

    2010-12-01

    Self-reported race/ethnicity is frequently used in epidemiological studies to assess an individual's background origin. However, in admixed populations such as Hispanic, self-reported race/ethnicity may not accurately represent them genetically because they are admixed with European, African and Native American ancestry. We estimated the proportions of genetic admixture in an ethnically diverse population of 396 mothers and 188 of their children with 35 ancestry informative markers (AIMs) using the STRUCTURE version 2.2 program. The majority of the markers showed significant deviation from Hardy-Weinberg equilibrium in our study population. In mothers self-identified as Black and White, the imputed ancestry proportions were 77.6% African and 75.1% European respectively, while the racial composition among self-identified Hispanics was 29.2% European, 26.0% African, and 44.8% Native American. We also investigated the utility of AIMs by showing the improved fitness of models in paraoxanase-1 genotype-phenotype associations after incorporating AIMs; however, the improvement was moderate at best. In summary, a minimal set of 35 AIMs is sufficient to detect population stratification and estimate the proportion of individual genetic admixture; however, the utility of these markers remains questionable.

  16. Ancestry, admixture and fitness in Colombian genomes

    PubMed Central

    Rishishwar, Lavanya; Conley, Andrew B.; Wigington, Charles H.; Wang, Lu; Valderrama-Aguirre, Augusto; King Jordan, I.

    2015-01-01

    The human dimension of the Columbian Exchange entailed substantial genetic admixture between ancestral source populations from Africa, the Americas and Europe, which had evolved separately for many thousands of years. We sought to address the implications of the creation of admixed American genomes, containing novel allelic combinations, for human health and fitness via analysis of an admixed Colombian population from Medellin. Colombian genomes from Medellin show a wide range of three-way admixture contributions from ancestral source populations. The primary ancestry component for the population is European (average = 74.6%, range = 45.0%–96.7%), followed by Native American (average = 18.1%, range = 2.1%–33.3%) and African (average = 7.3%, range = 0.2%–38.6%). Locus-specific patterns of ancestry were evaluated to search for genomic regions that are enriched across the population for particular ancestry contributions. Adaptive and innate immune system related genes and pathways are particularly over-represented among ancestry-enriched segments, including genes (HLA-B and MAPK10) that are involved in defense against endemic pathogens such as malaria. Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous glands (EDAR) are also found in regions with anomalous ancestry patterns. These results suggest the possibility that ancestry-specific loci were differentially retained in the modern admixed Colombian population based on their utility in the New World environment. PMID:26197429

  17. DNA polymorphism and selection at the melanocortin-1 receptor gene in normally pigmented southern African individuals.

    PubMed

    John, Premila R; Makova, Kateryna; Li, Wen-Hsiung; Jenkins, Trefor; Ramsay, Michele

    2003-06-01

    Skin pigmentation is a polygenic multifactorial trait determined by the cumulative effects of multiple genetic variants and environmental factors. Melanocortin-1 receptor (MC1R) is one of the genes involved in pigmentation, and has been implicated in the red hair and pale skin phenotype in human Caucasoid individuals. The present study was undertaken to identify variation at the MC1R locus in normally pigmented individuals in two African populations, sub-Saharan Negroids (22 unrelated individuals) and the San (17 unrelated individuals). The study showed considerable MC1R gene sequence variation with the detection of eight synonymous and three nonsynonymous mutations. This is the first report of nonsynonymous mutations in African individuals in the MC1R gene: L99I was found in a single San individual, S47I was detected in a single Negroid individual, and F196L was detected in five Negroid individuals (5/44; 0.11). The functional significance of these mutations is not known. Three of the eight synonymous mutations found, L106L (CTG --> CTA), F300F (TTC --> TTT), and T314T (ACA --> ACG) (also known as A942G), have been reported previously. T314T was the only variant that showed a significant difference between the Negroid and San populations (0.477 and 0.059, respectively; P = 1.6 x 10(-5)). Its low frequency in the San may be the result of random genetic drift in a population of small size, or selection. Several tests of neutrality of the MC1R coding region in these and other African populations were significant, suggesting that purifying selection (functional constraint) had occurred at this gene locus in Africans. This demonstrates that although some nonsynonymous MC1R mutations are tolerated in individuals with dark skin, this gene has likely played a significant role in the maintenance of dark pigmentation in Africans and normal pigment variation in non-African populations.

  18. Genetic ancestry of a Moroccan population as inferred from autosomal STRs

    PubMed Central

    Bentayebi, K.; Abada, F.; Ihzmad, H.; Amzazi, S.

    2014-01-01

    Detecting population substructure and ancestry is a critical issue for both association studies of health behaviors and forensic genetics. Determining aspects of a population's genetic history as potential sources of substructure can aid in design of future genetic studies. Within this context, fifteen autosomal short tandem repeat (STR), were used to examine population genetic structure and hypotheses of the origin of the modern Moroccan population from individuals belonging to three different ethnical groups from Morocco (Arab, Berber and Sahrawi), by comparing their autosomal STR variation with that of neighboring and non-neighboring populations in North Africa, Europe and Middle East as well as proposed ancestral populations in Morocco (Berber). We report on the results that the gradient of North African ancestry accounts for previous observations of low levels of sharing with Near East and a substantially increased gene flow especially from Morocco and Spain. PMID:25606427

  19. Afro-derived Amazonian populations: inferring continental ancestry and population substructure.

    PubMed

    Lopes Maciel, Luana Gomes; Ribeiro Rodrigues, Elzemar Martins; Carneiro Dos Santos, Ney Pereira; Ribeiro Dos Santos, Ândrea; Guerreiro, João Farias; Santos, Sidney

    2011-10-01

    A panel of Ancestry Informative Markers (AIMs) was used to identify population substructure and estimate individual and overall interethnic admixture in 294 individuals from seven African-derived communities of the Brazilian Amazon. A panel of 48 biallelic markers, representing the insertion (IN) or the deletion (DEL) of small DNA fragments, was employed for this purpose. Overall interethnic admixture estimates showed high miscegenation with other ethnic groups in all populations (between 46% and 64%). The proportion of ancestral genes varied significantly among individuals of the sample: the contribution of African genes varied between 12% and 75%; of European genes between 10% and 73%; and of Amerindians genes between 8% and 66%. The obtained data reveal a high contribution of Amerindian genes in these communities, unlike in other African-derived communities of the Northeast and the South of Brazil. In addition, the majority of the Amerindian contribution may result from the preferential inclusion of indigenous women in the African descent groups. High heterogeneity of the proportion of interethnic admixture among analyzed individuals was found when the proportion of ancestral genes of each individual of the sample was estimated. This heterogeneity is reflected in the fact that four populations can be considered as substructured and that the global African descent sample is possibly formed by two subpopulations.

  20. Mitochondrial and Y chromosome haplotype motifs as diagnostic markers of Jewish ancestry: a reconsideration.

    PubMed

    Tofanelli, Sergio; Taglioli, Luca; Bertoncini, Stefania; Francalacci, Paolo; Klyosov, Anatole; Pagani, Luca

    2014-01-01

    Several authors have proposed haplotype motifs based on site variants at the mitochondrial genome (mtDNA) and the non-recombining portion of the Y chromosome (NRY) to trace the genealogies of Jewish people. Here, we analyzed their main approaches and test the feasibility of adopting motifs as ancestry markers through construction of a large database of mtDNA and NRY haplotypes from public genetic genealogical repositories. We verified the reliability of Jewish ancestry prediction based on the Cohen and Levite Modal Haplotypes in their "classical" 6 STR marker format or in the "extended" 12 STR format, as well as four founder mtDNA lineages (HVS-I segments) accounting for about 40% of the current population of Ashkenazi Jews. For this purpose we compared haplotype composition in individuals of self-reported Jewish ancestry with the rest of European, African or Middle Eastern samples, to test for non-random association of ethno-geographic groups and haplotypes. Overall, NRY and mtDNA based motifs, previously reported to differentiate between groups, were found to be more represented in Jewish compared to non-Jewish groups. However, this seems to stem from common ancestors of Jewish lineages being rather recent respect to ancestors of non-Jewish lineages with the same "haplotype signatures." Moreover, the polyphyly of haplotypes which contain the proposed motifs and the misuse of constant mutation rates heavily affected previous attempts to correctly dating the origin of common ancestries. Accordingly, our results stress the limitations of using the above haplotype motifs as reliable Jewish ancestry predictors and show its inadequacy for forensic or genealogical purposes.

  1. Development of a Panel of Genome-Wide Ancestry Informative Markers to Study Admixture Throughout the Americas

    PubMed Central

    Galanter, Joshua Mark; Fernandez-Lopez, Juan Carlos; Gignoux, Christopher R.; Barnholtz-Sloan, Jill; Fernandez-Rozadilla, Ceres; Via, Marc; Hidalgo-Miranda, Alfredo; Contreras, Alejandra V.; Figueroa, Laura Uribe; Raska, Paola; Jimenez-Sanchez, Gerardo; Silva Zolezzi, Irma; Torres, Maria; Ponte, Clara Ruiz; Ruiz, Yarimar; Salas, Antonio; Nguyen, Elizabeth; Eng, Celeste; Borjas, Lisbeth; Zabala, William; Barreto, Guillermo; Rondón González, Fernando; Ibarra, Adriana; Taboada, Patricia; Porras, Liliana; Moreno, Fabián; Bigham, Abigail; Gutierrez, Gerardo; Brutsaert, Tom; León-Velarde, Fabiola; Moore, Lorna G.; Vargas, Enrique; Cruz, Miguel; Escobedo, Jorge; Rodriguez-Santana, José; Rodriguez-Cintrón, William; Chapela, Rocio; Ford, Jean G.; Bustamante, Carlos; Seminara, Daniela; Shriver, Mark; Ziv, Elad; Gonzalez Burchard, Esteban; Haile, Robert

    2012-01-01

    Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R2>0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region. PMID:22412386

  2. Photo-Realistic Statistical Skull Morphotypes: New Exemplars for Ancestry and Sex Estimation in Forensic Anthropology.

    PubMed

    Caple, Jodi; Stephan, Carl N

    2016-12-01

    Graphic exemplars of cranial sex and ancestry are essential to forensic anthropology for standardizing casework, training analysts, and communicating group trends. To date, graphic exemplars have comprised hand-drawn sketches, or photographs of individual specimens, which risks bias/subjectivity. Here, we performed quantitative analysis of photographic data to generate new photo-realistic and objective exemplars of skull form. Standardized anterior and left lateral photographs of skulls for each sex were analyzed in the computer graphics program Psychomorph for the following groups: South African Blacks, South African Whites, American Blacks, American Whites, and Japanese. The average cranial form was calculated for each photographic view, before the color information for every individual was warped to the average form and combined to produce statistical averages. These mathematically derived exemplars-and their statistical exaggerations or extremes-retain the high-resolution detail of the original photographic dataset, making them the ideal casework and training reference standards.

  3. Genomic Ancestry, Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing

    PubMed Central

    Lima-Costa, M. Fernanda; Macinko, James; Mambrini, Juliana Vaz de Melo; Cesar, Cibele C.; Peixoto, Sérgio V.; Magalhães, Wagner C. S.; Horta, Bernardo L.; Barreto, Mauricio; Castro-Costa, Erico; Firmo, Josélia O. A.; Proietti, Fernando A.; Leal, Thiago Peixoto; Rodrigues, Maira R.; Pereira, Alexandre; Tarazona-Santos, Eduardo

    2015-01-01

    Background Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. Materials/Methods We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality. Results European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups. Conclusions Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry—and the inverse for European ancestry—were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality. PMID:26680774

  4. Surgical anatomy of the pudendal nerve and its branches in South Africans.

    PubMed

    van der Walt, S; Oettlé, A C; Patel, H R H

    2015-07-01

    Dissection of the pudendal nerve (PN) and its branches in 71 cadavers revealed anatomic variations not previously described. Knowledge of this variation is necessary to prevent nerve injury resulting in sexual of sensory dysfunction. Because descriptions vary, this study re-evaluated the anatomy of the PN as implicated in perineal procedures in South Africans. The course of the PN from the gluteal region into the perineum was dissected in an adult sample of both sexes and of African and European ancestry. Distances between PN and branches to applicable landmarks were measured. Basic descriptive statistics and comparisons were carried out between groups. In 5/13 African females, the inferior rectal nerve (IRN) entered the gluteal region separately and in 12/13 cases it passed medial to the ischial spine with the PN. The dorsal nerve of the clitoris or penis (DNC/DNP) was closer to the bony frame in those of European ancestry. The IRN branches were more superficial in females, but deeper in males of European ancestry. In African females, a PN block and Richter stitch should be placed more medial. Outside-in transobturator tape procedures might endanger the DNC/DNP in obese individuals. In females of European ancestry the IRN branches are compromised during ischioanal abscess drainage. In males of European ancestry, the dorsal penile nerve block might be less effective. Predictions should be verified clinically.

  5. Uniparental ancestry markers in Chilean populations

    PubMed Central

    Vieira-Machado, Camilla Dutra; Tostes, Maluah; Alves, Gabrielle; Nazer, Julio; Martinez, Liliana; Wettig, Elisabeth; Pizarro Rivadeneira, Oscar; Diaz Caamaño, Marcela; Larenas Ascui, Jessica; Pavez, Pedro; Dutra, Maria da Graça; Castilla, Eduardo Enrique; Orioli, Ieda Maria

    2016-01-01

    Abstract The presence of Native Americans, Europeans, and Africans has led to the development of a multi-ethnic, admixed population in Chile. This study aimed to contribute to the characterization of the uniparental genetic structure of three Chilean regions. Newborns from seven hospitals in Independencia, Providencia, Santiago, Curicó, Cauquenes, Valdívia, and Puerto Montt communes, belonging to the Chilean regions of Santiago, Maule, and Los Lagos, were studied. The presence of Native American mitochondrial DNA (mtDNA) haplogroups and two markers present in the non-recombinant region of the Y chromosome, DYS199 and DYS287, indicative of Native American and African ancestry, respectively, was determined. A high Native American matrilineal contribution and a low Native American and African patrilineal contributions were found in all three studied regions. As previously found in Chilean admixed populations, the Native American matrilineal contribution was lower in Santiago than in the other studied regions. However, there was an unexpectedly higher contribution of Native American ancestry in one of the studied communes in Santiago, probably due to the high rate of immigration from other regions of the country. The population genetic sub-structure we detected in Santiago using few uniparental markers requires further confirmation, owing to possible stratification for autosomal and X-chromosome markers. PMID:27561109

  6. Placing the burden on the individual: overweight and obesity in African American and mainstream women's magazines.

    PubMed

    Campo, Shelly; Mastin, Teresa

    2007-01-01

    One third of all U.S. adult women, and more than 75% of African American women, are overweight or obese. This study examined overweight and obesity editorial content (N=406) in three mainstream and three African American women's magazines between 1984 and 2004. Content analysis was used to determine which strategies were suggested regarding diet, overweight, and obesity, which components of social cognitive theory were offered (behavior, person, or environment), and whether or not there were differences in the genres. The results suggest that although a wide range of strategies were being offered, the vast majority were behavioral changes with an individual solution focus. Although African American and mainstream magazines suggested many of the same strategies, nearly half more frequently appeared in one or the other genre. Mainstream magazines were twice as likely to offer the limiting or eliminating of fast food or junk food, eating more protein, eating lower-fat foods, and eating smaller portions. African American magazines were much more likely to cover fad diets and to suggest readers rely on God or faith in their diet plans. The average number of strategies offered per article was significantly higher in mainstream than in African American magazines.

  7. Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

    PubMed Central

    Banda, Yambazi; Kvale, Mark N.; Hoffmann, Thomas J.; Hesselson, Stephanie E.; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A.; Dispensa, Brad P.; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H.; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P.; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C.; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P.; Van Den Eeden, Stephen K.; Walter, Lawrence; Whitmer, Rachel A.; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

    2015-01-01

    Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian–European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent–child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent–child pairs was largely due to intermarriage. The parent–child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. PMID:26092716

  8. Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.

    PubMed

    Banda, Yambazi; Kvale, Mark N; Hoffmann, Thomas J; Hesselson, Stephanie E; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A; Dispensa, Brad P; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P; Van Den Eeden, Stephen K; Walter, Lawrence; Whitmer, Rachel A; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

    2015-08-01

    Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to intermarriage. The parent-child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies.

  9. Discovering genetic ancestry using spectral graph theory.

    PubMed

    Lee, Ann B; Luca, Diana; Klei, Lambertus; Devlin, Bernie; Roeder, Kathryn

    2010-01-01

    As one approach to uncovering the genetic underpinnings of complex disease, individuals are measured at a large number of genetic variants (usually SNPs) across the genome and these SNP genotypes are assessed for association with disease status. We propose a new statistical method called Spectral-GEM for the analysis of genome-wide association studies; the goal of Spectral-GEM is to quantify the ancestry of the sample from such genotypic data. Ignoring structure due to differential ancestry can lead to an excess of spurious findings and reduce power. Ancestry is commonly estimated using the eigenvectors derived from principal component analysis (PCA). To develop an alternative to PCA we draw on connections between multidimensional scaling and spectral graph theory. Our approach, based on a spectral embedding derived from the normalized Laplacian of a graph, can produce more meaningful delineation of ancestry than by using PCA. Often the results from Spectral-GEM are straightforward to interpret and therefore useful in association analysis. We illustrate the new algorithm with an analysis of the POPRES data [Nelson et al., 2008].

  10. Unravelling the hidden ancestry of American admixed populations

    PubMed Central

    Montinaro, Francesco; Busby, George B.J.; Pascali, Vincenzo L.; Myers, Simon; Hellenthal, Garrett; Capelli, Cristian

    2015-01-01

    The movement of people into the Americas has brought different populations into contact, and contemporary American genomes are the product of a range of complex admixture events. Here we apply a haplotype-based ancestry identification approach to a large set of genome-wide SNP data from a variety of American, European and African populations to determine the contributions of different ancestral populations to the Americas. Our results provide a fine-scale characterization of the source populations, identify a series of novel, previously unreported contributions from Africa and Europe and highlight geohistorical structure in the ancestry of American admixed populations. PMID:25803618

  11. Unravelling the hidden ancestry of American admixed populations.

    PubMed

    Montinaro, Francesco; Busby, George B J; Pascali, Vincenzo L; Myers, Simon; Hellenthal, Garrett; Capelli, Cristian

    2015-03-24

    The movement of people into the Americas has brought different populations into contact, and contemporary American genomes are the product of a range of complex admixture events. Here we apply a haplotype-based ancestry identification approach to a large set of genome-wide SNP data from a variety of American, European and African populations to determine the contributions of different ancestral populations to the Americas. Our results provide a fine-scale characterization of the source populations, identify a series of novel, previously unreported contributions from Africa and Europe and highlight geohistorical structure in the ancestry of American admixed populations.

  12. Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry.

    PubMed

    Ramos, Bruna Ribeiro de Andrade; D'Elia, Maria Paula Barbieri; Amador, Marcos Antônio Trindade; Santos, Ney Pereira Carneiro; Santos, Sidney Emanuel Batista; da Cruz Castelli, Erick; Witkin, Steven S; Miot, Hélio Amante; Miot, Luciane Donida Bartoli; da Silva, Márcia Guimarães

    2016-06-01

    Ancestry information can be useful in investigations of diseases with a genetic or infectious background. As the Brazilian population is highly admixed physical traits tend to be poor indicators of ancestry. The assessment of ancestry by ancestry informative markers (AIMs) can exclude the subjectivity of self-declared ethnicity and reported family origin. We aimed to evaluate the reliability of self-reported ethnicity or reported family origin as indicators of genomic ancestry in a female population from the Southeast of Brazil. Two cohorts were included: 404 women asked to self-report their ethnicity (Pop1) and 234 women asked to report their family's origin (Pop2). Identification of AIMs was performed using a panel of 61 markers and results were plotted against parental populations-Amerindian, Western European and Sub-Saharan African-using Structure v2.3.4. In Pop1 57.4 % of women self-reported as white, 34.6 % as brown and 8.0 % as black. Median global European, Amerindian and African contributions were 66.8, 12.6 and 16.6 %. In Pop2, 66.4 % of women declared European origin, 23.9 % African origin and 26.9 % Amerindian. Median global European, Amerindian and African contributions were 80.8, 7.3 and 7.6 %, respectively. Only 31.0 and 21.0 % of the global variation in African and European contributions, respectively, could be explained by self-reported ethnicity and reported family origin only accounted for 20.0 and 5.0 % of the variations observed in African and European ancestries, respectively. Amerindian ancestry did not influence self-reported ethnicity or declared family origin. Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry in these Brazilian populations.

  13. Beta-globin haplotype analysis suggests that a major source of Malagasy ancestry is derived from Bantu-speaking Negroids.

    PubMed

    Hewitt, R; Krause, A; Goldman, A; Campbell, G; Jenkins, T

    1996-06-01

    The origins of the inhabitants of Madagascar have not been fully resolved. Anthropological studies and preliminary genetic data point to two main sources of ancestry of the Malagasy, namely, Indonesian and African, with additional contributions from India and Arabia. The sickle-cell (beta s) mutation is found in populations of African and Indian origin. The frequency of the beta s-globin gene, derived from 1,425 Malagasy individuals, varies from 0 in some highland populations to .25 in some coastal populations. The beta s mutation is thought to have arisen at least five times, on the basis of the presence of five distinct beta s-associated haplotypes, each found in a separate geographic area. Twenty-five of the 35 Malagasy beta s haplotypes were of the typical "Bantu" type, 1 "Senegal" haplotype was found, and 2 rare or atypical haplotypes were observed; the remaining 7 haplotypes were consistent with the Bantu haplotype. The Bantu beta s mutation is thought to have been introduced into Madagascar by Bantu-speaking immigrants (colonists or slaves) from central or east Africa. The Senegal beta s mutation may have been introduced to the island via Portuguese naval explorers. This study provides the first definitive biological evidence that a major component of Malagasy ancestry is derived from African populations, in particular, Bantu-speaking Negroids. beta A haplotypes are also consistent with the claim for a significant African contribution to Malagasy ancestry but are also suggestive of Asian/Oceanic and Caucasoid admixture within the Malagasy population.

  14. RFMix: a discriminative modeling approach for rapid and robust local-ancestry inference.

    PubMed

    Maples, Brian K; Gravel, Simon; Kenny, Eimear E; Bustamante, Carlos D

    2013-08-08

    Local-ancestry inference is an important step in the genetic analysis of fully sequenced human genomes. Current methods can only detect continental-level ancestry (i.e., European versus African versus Asian) accurately even when using millions of markers. Here, we present RFMix, a powerful discriminative modeling approach that is faster (~30×) and more accurate than existing methods. We accomplish this by using a conditional random field parameterized by random forests trained on reference panels. RFMix is capable of learning from the admixed samples themselves to boost performance and autocorrect phasing errors. RFMix shows high sensitivity and specificity in simulated Hispanics/Latinos and African Americans and admixed Europeans, Africans, and Asians. Finally, we demonstrate that African Americans in HapMap contain modest (but nonzero) levels of Native American ancestry (~0.4%).

  15. Ancient west Eurasian ancestry in southern and eastern Africa

    PubMed Central

    Pickrell, Joseph K.; Patterson, Nick; Loh, Po-Ru; Lipson, Mark; Berger, Bonnie; Stoneking, Mark; Pakendorf, Brigitte; Reich, David

    2014-01-01

    The history of southern Africa involved interactions between indigenous hunter–gatherers and a range of populations that moved into the region. Here we use genome-wide genetic data to show that there are at least two admixture events in the history of Khoisan populations (southern African hunter–gatherers and pastoralists who speak non-Bantu languages with click consonants). One involved populations related to Niger–Congo-speaking African populations, and the other introduced ancestry most closely related to west Eurasian (European or Middle Eastern) populations. We date this latter admixture event to ∼900–1,800 y ago and show that it had the largest demographic impact in Khoisan populations that speak Khoe–Kwadi languages. A similar signal of west Eurasian ancestry is present throughout eastern Africa. In particular, we also find evidence for two admixture events in the history of Kenyan, Tanzanian, and Ethiopian populations, the earlier of which involved populations related to west Eurasians and which we date to ∼2,700–3,300 y ago. We reconstruct the allele frequencies of the putative west Eurasian population in eastern Africa and show that this population is a good proxy for the west Eurasian ancestry in southern Africa. The most parsimonious explanation for these findings is that west Eurasian ancestry entered southern Africa indirectly through eastern Africa. PMID:24550290

  16. Accuracy Rates of Ancestry Estimation by Forensic Anthropologists Using Identified Forensic Cases.

    PubMed

    Thomas, Richard M; Parks, Connie L; Richard, Adam H

    2017-01-30

    A common task in forensic anthropology involves the estimation of the ancestry of a decedent by comparing their skeletal morphology and measurements to skeletons of individuals from known geographic groups. However, the accuracy rates of ancestry estimation methods in actual forensic casework have rarely been studied. This article uses 99 forensic cases with identified skeletal remains to develop accuracy rates for ancestry estimations conducted by forensic anthropologists. The overall rate of correct ancestry estimation from these cases is 90.9%, which is comparable to most research-derived rates and those reported by individual practitioners. Statistical tests showed no significant difference in accuracy rates depending on examiner education level or on the estimated or identified ancestry. More recent cases showed a significantly higher accuracy rate. The incorporation of metric analyses into the ancestry estimate in these cases led to a higher accuracy rate.

  17. Genomic ancestry as a predictor of haemodynamic profile in heart failure

    PubMed Central

    Bernardez-Pereira, Sabrina; Gioli-Pereira, Luciana; Marcondes-Braga, Fabiana G; Santos, Paulo Caleb Junior Lima; Spina, Joceli Mabel Rocha; Horimoto, Andréa Roseli Vançan Russo; Santos, Hadassa Campos; Bacal, Fernando; Fernandes, Fábio; Mansur, Alfredo Jose; Pietrobon, Ricardo; Krieger, José Eduardo; Mesquita, Evandro Tinoco; Pereira, Alexandre Costa

    2016-01-01

    Objective The aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF). Methods Observational, cross-sectional study. Eligible participants were aged between 18 and 80 years; ejection fraction was ≤50%. Patients underwent genetic analysis of ancestry informative markers, echocardiography and impedance cardiography (ICG). Race was determined by self-classification into two groups: white and non-white. Genomic ancestry was estimated using a panel of 101 348 polymorphic markers and three continental reference populations (European, African and Native American). Results Our study included 362 patients with HF between August 2012 and August 2014. 123 patients with HF declared themselves as white and 234 patients declared themselves as non-white. No statistically significant differences were found regarding the ICG parameters according to self-declared race. The Amerindian ancestry was positively correlated with systolic time ratio (r=0.109, p<0.05). The thoracic fluid content index (r=0.124. p<0.05), E wave peak (r=0.127. p<0.05) and E/e′ ratio (r=0.197. p<0.01) were correlated positively with African ancestry. In multiple linear regression, African ancestry remained associated with the E/e′ ratio, even after adjustment to risk factors. Conclusions The African genetic ancestry was associated with worse parameters of diastolic function; the Amerindian ancestry correlated with a worse pattern of ventricular contractility, while self-declared colour was not helpful to infer haemodynamic profiles in HF. Trials registration number NTC02043431. PMID:27547430

  18. Ancestry informative markers clarify the regional admixture variation in the Costa Rican population.

    PubMed

    Cámpos-Sanchez, Rebeca; Raventós, Henriette; Barrantes, Ramiro

    2013-10-01

    The genetic structure of Costa Rica's population is complex, both by region and by individual, due to the admixture process that started during the 15th century and historical events thereafter. Previous studies have been done mostly on Amerindian populations and the Central Valley inhabitants using various microsatellites and mitochondrial DNA markers. Here, we study for the first time a random sample from all regions of the country with ancestry informative markers (AIMs) to address the individual and regional admixture proportions. A sample of 160 male individuals was screened for 78 AIMs customized in a GoldenGate platform from Illumina. We observed that this small set of AIMs has the same power of hundreds of microsatellites and thousands of single-nucleotide polymorphisms to evaluate admixture, with the benefit of reducing genotyping costs. This type of investigation is necessary to explore new genetic markers useful for forensic and genetic investigation. Our data showed a mean admixture proportion of 49.2% European (EUR), 37.8% Native American (NAM), and 12.9% African (AFR), with a disproportionate admixture composition by region. In addition, when Chinese (CHB) was included as a fourth component, the proportions changed to 45.6% EUR, 33.5% NAM, 11.7% AFR, and 9.2% CHB. The admixture trend is consistent among all regions (EUR > NAM > AFR), and individual admixture estimates vary broadly in each region. Though we did not find stratification in Costa Rica's population, gene admixture should be evaluated in future genetic studies of Costa Rica, especially for the Caribbean region, as it contains the largest proportion of African ancestry (30.9%).

  19. The landscape of recombination in African Americans.

    PubMed

    Hinch, Anjali G; Tandon, Arti; Patterson, Nick; Song, Yunli; Rohland, Nadin; Palmer, Cameron D; Chen, Gary K; Wang, Kai; Buxbaum, Sarah G; Akylbekova, Ermeg L; Aldrich, Melinda C; Ambrosone, Christine B; Amos, Christopher; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bock, Cathryn H; Boerwinkle, Eric; Cai, Qiuyin; Caporaso, Neil; Casey, Graham; Cupples, L Adrienne; Deming, Sandra L; Diver, W Ryan; Divers, Jasmin; Fornage, Myriam; Gillanders, Elizabeth M; Glessner, Joseph; Harris, Curtis C; Hu, Jennifer J; Ingles, Sue A; Isaacs, William; John, Esther M; Kao, W H Linda; Keating, Brendan; Kittles, Rick A; Kolonel, Laurence N; Larkin, Emma; Le Marchand, Loic; McNeill, Lorna H; Millikan, Robert C; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; Nyante, Sarah; Papanicolaou, George J; Press, Michael F; Psaty, Bruce M; Reiner, Alex P; Rich, Stephen S; Rodriguez-Gil, Jorge L; Rotter, Jerome I; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret; Strom, Sara S; Thun, Michael J; Tucker, Margaret A; Wang, Zhaoming; Wiencke, John K; Witte, John S; Wrensch, Margaret; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A; Zheng, Wei; Ziegler, Regina G; Zhu, Xiaofeng; Redline, Susan; Hirschhorn, Joel N; Henderson, Brian E; Taylor, Herman A; Price, Alkes L; Hakonarson, Hakon; Chanock, Stephen J; Haiman, Christopher A; Wilson, James G; Reich, David; Myers, Simon R

    2011-07-20

    Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.

  20. Biogeographical ancestry and race.

    PubMed

    Gannett, Lisa

    2014-09-01

    The use of racial and ethnic categories in biological and biomedical research is controversial-for example, in the comparison of disease risk in different groups or as a means of making use of or controlling for population structure in the mapping of genes to chromosomes. Biogeographical ancestry (BGA) has been recommended as a more accurate and appropriate category. BGA is a product of the collaboration between biological anthropologist Mark Shriver from Pennsylvania State University and molecular biologist Tony Frudakis from the now-defunct biotechnology start-up company DNAPrint genomics, Inc. Shriver and Frudakis portray BGA as a measure of the 'biological', 'genetic', 'natural', and 'objective' components of race and ethnicity, what philosophers of science would call a natural kind. This paper argues that BGA is not a natural kind that escapes social and political connotations of race and ethnicity, as Shriver and Frudakis and other proponents believe, but a construction that is built upon race-as race has been socially constructed in the European scientific and philosophical traditions. More specifically, BGA is not a global category of biological and anthropological classification but a local category shaped by the U.S. context of its production, especially the forensic aim of being able to predict the race or ethnicity of an unknown suspect based on DNA found at the crime scene. Therefore, caution needs to be exercised in the embrace of BGA as an alternative to the use of racial and ethnic categories in biological and biomedical research.

  1. Accurate inference of local phased ancestry of modern admixed populations.

    PubMed

    Ma, Yamin; Zhao, Jian; Wong, Jian-Syuan; Ma, Li; Li, Wenzhi; Fu, Guoxing; Xu, Wei; Zhang, Kui; Kittles, Rick A; Li, Yun; Song, Qing

    2014-07-23

    Population stratification is a growing concern in genetic-association studies. Averaged ancestry at the genome level (global ancestry) is insufficient for detecting the population substructures and correcting population stratifications in association studies. Local and phase stratification are needed for human genetic studies, but current technologies cannot be applied on the entire genome data due to various technical caveats. Here we developed a novel approach (aMAP, ancestry of Modern Admixed Populations) for inferring local phased ancestry. It took about 3 seconds on a desktop computer to finish a local ancestry analysis for each human genome with 1.4-million SNPs. This method also exhibits the scalability to larger datasets with respect to the number of SNPs, the number of samples, and the size of reference panels. It can detect the lack of the proxy of reference panels. The accuracy was 99.4%. The aMAP software has a capacity for analyzing 6-way admixed individuals. As the biomedical community continues to expand its efforts to increase the representation of diverse populations, and as the number of large whole-genome sequence datasets continues to grow rapidly, there is an increasing demand on rapid and accurate local ancestry analysis in genetics, pharmacogenomics, population genetics, and clinical diagnosis.

  2. High interpopulation homogeneity in Central Argentina as assessed by Ancestry Informative Markers (AIMs).

    PubMed

    García, Angelina; Dermarchi, Darío A; Tovo-Rodrigues, Luciana; Pauro, Maia; Callegari-Jacques, Sidia M; Salzano, Francisco M; Hutz, Mara H

    2015-01-01

    The population of Argentina has already been studied with regard to several genetic markers, but much more data are needed for the appropriate definition of its genetic profile. This study aimed at investigating the admixture patterns and genetic structure in Central Argentina, using biparental markers and comparing the results with those previously obtained by us with mitochondrial DNA (mtDNA) in the same samples. A total of 521 healthy unrelated individuals living in 13 villages of the Córdoba and San Luis provinces were tested. The individuals were genotyped for ten autosomal ancestry informative markers (AIMs). Allele frequencies were compared with those of African, European and Native American populations, chosen to represent parental contributions. The AIM estimates indicated a greater influence of the Native American ancestry as compared to previous studies in the same or other Argentinean regions, but smaller than that observed with the mtDNA tests. These differences can be explained, respectively, by different genetic contributions between rural and urban areas, and asymmetric gene flow occurred in the past. But a most unexpected finding was the marked interpopulation genetic homogeneity found in villages located in diverse geographic environments across a wide territory, suggesting considerable gene flow.

  3. High interpopulation homogeneity in Central Argentina as assessed by Ancestry Informative Markers (AIMs)

    PubMed Central

    García, Angelina; Dermarchi, Darío A.; Tovo-Rodrigues, Luciana; Pauro, Maia; Callegari-Jacques, Sidia M.; Salzano, Francisco M.; Hutz, Mara H.

    2015-01-01

    The population of Argentina has already been studied with regard to several genetic markers, but much more data are needed for the appropriate definition of its genetic profile. This study aimed at investigating the admixture patterns and genetic structure in Central Argentina, using biparental markers and comparing the results with those previously obtained by us with mitochondrial DNA (mtDNA) in the same samples. A total of 521 healthy unrelated individuals living in 13 villages of the Córdoba and San Luis provinces were tested. The individuals were genotyped for ten autosomal ancestry informative markers (AIMs). Allele frequencies were compared with those of African, European and Native American populations, chosen to represent parental contributions. The AIM estimates indicated a greater influence of the Native American ancestry as compared to previous studies in the same or other Argentinean regions, but smaller than that observed with the mtDNA tests. These differences can be explained, respectively, by different genetic contributions between rural and urban areas, and asymmetric gene flow occurred in the past. But a most unexpected finding was the marked interpopulation genetic homogeneity found in villages located in diverse geographic environments across a wide territory, suggesting considerable gene flow. PMID:26500436

  4. Vocal individuality cues in the African penguin (Spheniscus demersus): a source-filter theory approach

    PubMed Central

    Favaro, Livio; Gamba, Marco; Alfieri, Chiara; Pessani, Daniela; McElligott, Alan G.

    2015-01-01

    The African penguin is a nesting seabird endemic to southern Africa. In penguins of the genus Spheniscus vocalisations are important for social recognition. However, it is not clear which acoustic features of calls can encode individual identity information. We recorded contact calls and ecstatic display songs of 12 adult birds from a captive colony. For each vocalisation, we measured 31 spectral and temporal acoustic parameters related to both source and filter components of calls. For each parameter, we calculated the Potential of Individual Coding (PIC). The acoustic parameters showing PIC ≥ 1.1 were used to perform a stepwise cross-validated discriminant function analysis (DFA). The DFA correctly classified 66.1% of the contact calls and 62.5% of display songs to the correct individual. The DFA also resulted in the further selection of 10 acoustic features for contact calls and 9 for display songs that were important for vocal individuality. Our results suggest that studying the anatomical constraints that influence nesting penguin vocalisations from a source-filter perspective, can lead to a much better understanding of the acoustic cues of individuality contained in their calls. This approach could be further extended to study and understand vocal communication in other bird species. PMID:26602001

  5. Vocal individuality cues in the African penguin (Spheniscus demersus): a source-filter theory approach.

    PubMed

    Favaro, Livio; Gamba, Marco; Alfieri, Chiara; Pessani, Daniela; McElligott, Alan G

    2015-11-25

    The African penguin is a nesting seabird endemic to southern Africa. In penguins of the genus Spheniscus vocalisations are important for social recognition. However, it is not clear which acoustic features of calls can encode individual identity information. We recorded contact calls and ecstatic display songs of 12 adult birds from a captive colony. For each vocalisation, we measured 31 spectral and temporal acoustic parameters related to both source and filter components of calls. For each parameter, we calculated the Potential of Individual Coding (PIC). The acoustic parameters showing PIC ≥ 1.1 were used to perform a stepwise cross-validated discriminant function analysis (DFA). The DFA correctly classified 66.1% of the contact calls and 62.5% of display songs to the correct individual. The DFA also resulted in the further selection of 10 acoustic features for contact calls and 9 for display songs that were important for vocal individuality. Our results suggest that studying the anatomical constraints that influence nesting penguin vocalisations from a source-filter perspective, can lead to a much better understanding of the acoustic cues of individuality contained in their calls. This approach could be further extended to study and understand vocal communication in other bird species.

  6. Distinct Transcript Isoforms of the Atypical Chemokine Receptor 1 (ACKR1) / Duffy Antigen Receptor for Chemokines (DARC) Gene Are Expressed in Lymphoblasts and Altered Isoform Levels Are Associated with Genetic Ancestry and the Duffy-Null Allele

    PubMed Central

    Davis, Melissa B.; Walens, Andrea; Hire, Rupali; Mumin, Kauthar; Brown, Andrea M.; Ford, DeJuana; Howerth, Elizabeth W.; Monteil, Michele

    2015-01-01

    The Atypical ChemoKine Receptor 1 (ACKR1) gene, better known as Duffy Antigen Receptor for Chemokines (DARC or Duffy), is responsible for the Duffy Blood Group and plays a major role in regulating the circulating homeostatic levels of pro-inflammatory chemokines. Previous studies have shown that one common variant, the Duffy Null (Fy-) allele that is specific to African Ancestry groups, completely removes expression of the gene on erythrocytes; however, these individuals retain endothelial expression. Additional alleles are associated with a myriad of clinical outcomes related to immune responses and inflammation. In addition to allele variants, there are two distinct transcript isoforms of DARC which are expressed from separate promoters, and very little is known about the distinct transcriptional regulation or the distinct functionality of these protein isoforms. Our objective was to determine if the African specific Fy- allele alters the expression pattern of DARC isoforms and therefore could potentially result in a unique signature of the gene products, commonly referred to as antigens. Our work is the first to establish that there is expression of DARC on lymphoblasts. Our data indicates that people of African ancestry have distinct relative levels of DARC isoforms expressed in these cells. We conclude that the expression of both isoforms in combination with alternate alleles yields multiple Duffy antigens in ancestry groups, depending upon the haplotypes across the gene. Importantly, we hypothesize that DARC isoform expression patterns will translate into ancestry-specific inflammatory responses that are correlated with the axis of pro-inflammatory chemokine levels and distinct isoform-specific interactions with these chemokines. Ultimately, this work will increase knowledge of biological mechanisms underlying disparate clinical outcomes of inflammatory-related diseases among ethnic and geographic ancestry groups. PMID:26473357

  7. A GWAS meta-analysis and replication study identifies a novel locus within CLPTM1L/TERT associated with nasopharyngeal carcinoma in individuals of Chinese ancestry

    PubMed Central

    Yu, Kai; Chin, Yoon-Ming; Lou, Pei-Jen; Hsu, Wan-Lun; McKay, James D.; Chen, Chien-Jen; Chang, Yu-Sun; Chen, Li-Zhen; Chen, Ming-Yuan; Cui, Qian; Feng, Fu-Tuo; Feng, Qi-Shen; Guo, Yun-Miao; Jia, Wei-Hua; Khoo, Alan Soo-Beng; Liu, Wen-Sheng; Mo, Hao-Yuan; Pua, Kin-Choo; Teo, Soo-Hwang; Tse, Ka-Po; Xia, Yun-Fei; Zhang, Hongxin; Zhou, Gang-Qiao; Liu, Jian-Jun; Zeng, Yi-Xin; Hildesheim, Allan

    2015-01-01

    Background Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied. Methods We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases;3,740 controls). 43 noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of 4 independent case-control studies across 3 regions in Asia (4,716 cases;5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. Results In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR=0.81;p-value 6.3*10−13). Our results also provide support for associations reported from published NPC GWAS - rs6774494 (p = 1.5*10−12;located in the MECOM gene region), rs9510787 (p = 5.0*10−10;located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (p = 2.8*10−8,p = 7.0*10−7,and p = 8.4*10−7 respectively;located in the CDKN2A/B gene region). Conclusion We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene is important for telomere maintenance and has been reported to be over-expressed in NPC, and an EBV protein expressed in NPC (LMP1) modulates TERT expression/telomerase activity. Impact Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis. PMID:26545403

  8. Ancestry, Temporality, and Potentiality

    PubMed Central

    Gibbon, Sahra

    2014-01-01

    In this paper I examine the variety of ways potential is articulated, entailed, and produced in how the field of cancer genetics is being constituted as a domain of transnational research and an emerging site of health-care intervention in southern Brazil. Drawing on analysis of fieldwork in Brazilian cancer-genetics clinics, I explore how different expressions of potential come to inform dynamically the pursuit of prevention, care, and research as diversely scaled investments for those working and living with cancer-genetics knowledge and technologies. It illustrates how specific temporalities help to constitute and “abductively” frame the meaning of these different potentials particularly as this relates to a focus on ancestry. Colonial histories of migration, the embodied effects of dietary habits, or the moral failings of near and distant ancestors as well as promissory futures and the contingency of lived lives become at different times templates for identifying, materializing, and transforming how the potential of cancer genetics in Brazil is articulated. Potential is also expressed through an idiom of “choice” in different efforts to situate participation in cancer-genetics research as prevention or to negotiate access to basic public health. I explore how these expressions of cancer genetics as potential powerfully yet unevenly work to sustain knowledge practices as well as propel patients and their families into fledgling domains of clinical practice and scientific research. At the same time there is always an “excess of meaning” in these endeavors that make visible lines of fracture and disjuncture in collective efforts to make future histories of and from the pursuit of cancer genetics in southern Brazil. PMID:25018561

  9. Red-ox speciation and mixing state of iron in individual African dust particles

    NASA Astrophysics Data System (ADS)

    Deboudt, Karine; Gloter, Alexandre; Mussi, Alexandre; Flament, Pascal

    2012-06-01

    The Fe distribution in African dust particles collected in Senegal (North-Western Africa) during the African Monsoon Multidisciplinary Analysis Special Observation Period 0 (AMMA-"SOP 0," February 2006) was assessed using individual particle analysis (Scanning and Transmission Electron Microscopy respectively equipped with X-ray Spectrometry (SEM-EDX) and Electron Energy Loss Spectrometry (TEM-EELS)). Senegal is not a dust source area; the chemical composition of collected dusts indicates that they originate primarily in the North-Western Sahara, which is consistent with previous studies of the area. Fe can be present inside dust particles as a substitution element in the crystalline lattice of aluminosilicate, but a high proportion (62%) of aluminosilicate Fe-containing particles are also found as an internal mixture of aluminosilicate with Fe oxide grains (including both oxide and hydroxide species). The 3D structure of such particles obtained by tomography reveals that these Fe-rich inclusions are often found at the surface of aluminosilicate particles but that some are also included inside particles. These Fe oxide grains can result from crustal earth or atmospheric processes during long-range transport. FeIII is dominant in both the aluminosilicate matrix and the Fe oxide grains (FeIII/Σ Fe ratio = 76.8% and 90.0%, respectively, on average), with notable heterogeneities of Fe valence inside grains at a nanometer scale.

  10. A Continuous Correlated Beta Process Model for Genetic Ancestry in Admixed Populations

    PubMed Central

    Gompert, Zachariah

    2016-01-01

    Admixture and recombination create populations and genomes with genetic ancestry from multiple source populations. Analyses of genetic ancestry in admixed populations are relevant for trait and disease mapping, studies of speciation, and conservation efforts. Consequently, many methods have been developed to infer genome-average ancestry and to deconvolute ancestry into continuous local ancestry blocks or tracts within individuals. Current methods for local ancestry inference perform well when admixture occurred recently or hybridization is ongoing, or when admixture occurred in the distant past such that local ancestry blocks have fixed in the admixed population. However, methods to infer local ancestry frequencies in isolated admixed populations still segregating for ancestry do not exist. In the current paper, I develop and test a continuous correlated beta process model to fill this analytical gap. The method explicitly models autocorrelations in ancestry frequencies at the population-level and uses discriminant analysis of SNP windows to take advantage of ancestry blocks within individuals. Analyses of simulated data sets show that the method is generally accurate such that ancestry frequency estimates exhibited low root-mean-square error and were highly correlated with the true values, particularly when large (±10 or ±20) SNP windows were used. Along these lines, the proposed method outperformed post hoc inference of ancestry frequencies from a traditional hidden Markov model (i.e., the linkage model in structure), particularly when admixture occurred more distantly in the past with little on-going gene flow or was followed by natural selection. The reliability and utility of the method was further assessed by analyzing genetic ancestry in an admixed human population (Uyghur) and three populations from a hybrid zone between Mus domesticus and M. musculus. Considerable variation in ancestry frequencies was detected within and among chromosomes in the Uyghur

  11. A Continuous Correlated Beta Process Model for Genetic Ancestry in Admixed Populations.

    PubMed

    Gompert, Zachariah

    2016-01-01

    Admixture and recombination create populations and genomes with genetic ancestry from multiple source populations. Analyses of genetic ancestry in admixed populations are relevant for trait and disease mapping, studies of speciation, and conservation efforts. Consequently, many methods have been developed to infer genome-average ancestry and to deconvolute ancestry into continuous local ancestry blocks or tracts within individuals. Current methods for local ancestry inference perform well when admixture occurred recently or hybridization is ongoing, or when admixture occurred in the distant past such that local ancestry blocks have fixed in the admixed population. However, methods to infer local ancestry frequencies in isolated admixed populations still segregating for ancestry do not exist. In the current paper, I develop and test a continuous correlated beta process model to fill this analytical gap. The method explicitly models autocorrelations in ancestry frequencies at the population-level and uses discriminant analysis of SNP windows to take advantage of ancestry blocks within individuals. Analyses of simulated data sets show that the method is generally accurate such that ancestry frequency estimates exhibited low root-mean-square error and were highly correlated with the true values, particularly when large (±10 or ±20) SNP windows were used. Along these lines, the proposed method outperformed post hoc inference of ancestry frequencies from a traditional hidden Markov model (i.e., the linkage model in structure), particularly when admixture occurred more distantly in the past with little on-going gene flow or was followed by natural selection. The reliability and utility of the method was further assessed by analyzing genetic ancestry in an admixed human population (Uyghur) and three populations from a hybrid zone between Mus domesticus and M. musculus. Considerable variation in ancestry frequencies was detected within and among chromosomes in the Uyghur

  12. Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

    PubMed Central

    Ghani, Mahdi; Reitz, Christiane; Cheng, Rong; Vardarajan, Badri Narayan; Jun, Gyungah; Sato, Christine; Naj, Adam; Rajbhandary, Ruchita; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick A.; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hendrie, Hugh; Hall, Kathleen S.; Goate, Alison M.; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Lee, Joseph H.; Schellenberg, Gerard D.; St. George-Hyslop, Peter; Mayeux, Richard; Rogaeva, Ekaterina

    2015-01-01

    IMPORTANCE Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer’s Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer’s Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03

  13. Selecting SNPs to Identify Ancestry

    PubMed Central

    Sampson, Joshua; Kidd, Kenneth K; Kidd, Judith R; Zhao, Hongyu

    2011-01-01

    Background/Aims An individual’s genotypes at a group of Single Nucleotide Polymorphisms (SNPs) can be used to predict that individual’s ethnicity, or ancestry. In medical studies, knowledge of a subject’s ancestry can minimize possible confounding, and in forensic applications, such knowledge can help direct investigations. Our goal is to select a small subset of SNPs, from the millions already identified in the human genome, that can predict ancestry with a minimal error rate. Methods The general form for this variable selection procedure is to estimate the expected error rates for sets of SNPs using a training dataset and consider those sets with the lowest error rates given their size. The quality of the estimate for the error rate determines the quality of the resulting SNPs. As the apparent error rate performs poorly when either the number of SNPs or the number of populations is large, we propose a new estimate, the Improved Bayesian Estimate. Conclusions We demonstrate that selection procedures based on this estimate produce small sets of SNPs that can accurately predict ancestry. We also provide a list of the 100 optimal SNPs for identifying ancestry. R functions are available at http://bioinformatics.med.yale.edu/group/josh/index.html. PMID:21668909

  14. The landscape of recombination in African Americans

    PubMed Central

    Hinch, Anjali G.; Tandon, Arti; Patterson, Nick; Song, Yunli; Rohland, Nadin; Palmer, Cameron D.; Chen, Gary K.; Wang, Kai; Buxbaum, Sarah G.; Akylbekova, Meggie; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Boerwinkle, Eric; Cai, Qiuyin; Caporaso, Neil; Casey, Graham; Cupples, L. Adrienne; Deming, Sandra L.; Diver, W. Ryan; Divers, Jasmin; Fornage, Myriam; Gillanders, Elizabeth M.; Glessner, Joseph; Harris, Curtis C.; Hu, Jennifer J.; Ingles, Sue A.; Isaacs, Williams; John, Esther M.; Kao, W. H. Linda; Keating, Brendan; Kittles, Rick A.; Kolonel, Laurence N.; Larkin, Emma; Le Marchand, Loic; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; Nyante, Sarah; Papanicolaou, George J.; Press, Michael F.; Psaty, Bruce M.; Reiner, Alex P.; Rich, Stephen S.; Rodriguez-Gil, Jorge L.; Rotter, Jerome I.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Thun, Michael J.; Tucker, Margaret A.; Wang, Zhaoming; Wiencke, John K.; Witte, John S.; Wrensch, Margaret; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Zhu, Xiaofeng; Redline, Susan; Hirschhorn, Joel N.; Henderson, Brian E.; Taylor, Herman A.; Price, Alkes L.; Hakonarson, Hakon; Chanock, Stephen J.; Haiman, Christopher A.; Wilson, James G.; Reich, David; Myers, Simon R.

    2011-01-01

    Recombination, together with mutation, is the ultimate source of genetic variation in populations. We leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing-over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P<10−245). We identify a 17 base pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of African-enriched alleles of PRDM9. PMID:21775986

  15. Men of African Descent and Carcinoma of the Prostate Consortium

    Cancer.gov

    The Men of African Descent and Carcinoma of the Prostate Consortium collaborates on epidemiologic studies to address the high burden of prostate cancer and to understand the causes of etiology and outcomes among men of African ancestry.

  16. Pre-Hispanic Mesoamerican demography approximates the present-day ancestry of Mestizos throughout the territory of Mexico.

    PubMed

    Rubi-Castellanos, Rodrigo; Martínez-Cortés, Gabriela; Muñoz-Valle, José Francisco; González-Martín, Antonio; Cerda-Flores, Ricardo M; Anaya-Palafox, Manuel; Rangel-Villalobos, Héctor

    2009-07-01

    Over the last 500 years, admixture among Amerindians, Europeans, and Africans, principally, has come to shape the present-day gene pool of Mexicans, particularly Mestizos, who represent about 93% of the total Mexican population. In this work, we analyze the genetic data of 13 combined DNA index system-short tandem repeats (CODIS-STRs) in 1,984 unrelated Mestizos representing 10 population samples from different regions of Mexico, namely North, West, Central, and Southeast. The analysis of molecular variance (AMOVA) test demonstrated low but significant differentiation among Mestizos from different regions (F(ST) = 0.34%; P = 0.0000). Although the spatial analysis of molecular variance (SAMOVA) predicted clustering Mestizo populations into four well-delimited groups, the main differentiation was observed between Northwest when compared with Central and Southeast regions. In addition, we included analysis of individuals of Amerindian (Purepechas), European (Huelva, Spain), and African (Fang) origin. Thus, STRUCTURE analysis was performed identifying three well-differentiated ancestral populations (k = 3). STRUCTURE results and admixture estimations by means of LEADMIX software in Mestizo populations demonstrated genetic heterogeneity or asymmetric admixture throughout Mexico, displaying an increasing North-to-South gradient of Amerindian ancestry, and vice versa regarding the European component. Interestingly, this distribution of Amerindian ancestry roughly reflects pre-Hispanic Native-population density, particularly toward the Mesoamerican area. The forensic, epidemiological, and evolutionary implications of these findings are discussed herein.

  17. HGDP and HapMap analysis by Ancestry Mapper reveals local and global population relationships.

    PubMed

    Magalhães, Tiago R; Casey, Jillian P; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J; Shah, Naisha; Sobral, João; Ennis, Sean

    2012-01-01

    Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set.

  18. HGDP and HapMap Analysis by Ancestry Mapper Reveals Local and Global Population Relationships

    PubMed Central

    Magalhães, Tiago R.; Casey, Jillian P.; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J.; Shah, Naisha; Sobral, João; Ennis, Sean

    2012-01-01

    Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set. PMID:23189146

  19. The Comparative Influence of Individual, Peer Tutoring, and Communal Learning Contexts on the Recall of African American Children.

    ERIC Educational Resources Information Center

    Dill, Ebony M.; Boykin, A. Wade

    2000-01-01

    Examined the effect of communal learning, peer tutoring, and individual learning on the text recall of African American fifth graders. Students completed surveys assessing their preference for communal beliefs and behaviors, participated in groups, and recalled text. Communal learning group students recalled the most text. Communal beliefs…

  20. Individual Factors Influencing Effective Nonviolent Behavior and Fighting in Peer Situations: A Qualitative Study with Urban African American Adolescents

    ERIC Educational Resources Information Center

    Farrell, Albert D.; Erwin, Elizabeth H.; Bettencourt, Amie; Mays, Sally; Vulin-Reynolds, Monique; Sullivan, Terri; Allison, Kevin W.; Kliewer, Wendy; Meyer, Aleta

    2008-01-01

    This qualitative study examined individual-level factors that influence adolescents' responses to problem situations involving peers. Interviews were conducted with 106 middle school students (97% African American) from an urban school system. Participants described factors that would make it easier and those that would make it more difficult for…

  1. Forensic genetic analysis of bio-geographical ancestry.

    PubMed

    Phillips, Chris

    2015-09-01

    With the great strides made in the last ten years in the understanding of human population variation and the detailed characterization of the genome, it is now possible to identify sets of ancestry informative markers suitable for relatively small-scale PCR-based assays and use them to analyze the ancestry of an individual from forensic DNA. This review outlines some of the current understanding of past human population structure and how it may have influenced the complex distribution of contemporary human diversity. A simplified description of human diversity can provide a suitable basis for choosing the best ancestry-informative markers, which is important given the constraints of multiplex sizes in forensic DNA tests. It is also important to decide the level of geographic resolution that is realistic to ensure the balance between informativeness and an over-simplification of complex human diversity patterns. A detailed comparison is made of the most informative ancestry markers suitable for forensic use and assessments are made of the data analysis regimes that can provide statistical inferences of a DNA donor's bio-geographical ancestry.

  2. Ancestry Estimation and Control of Population Stratification for Sequence-based Association Studies

    PubMed Central

    Wang, Chaolong; Zhan, Xiaowei; Bragg-Gresham, Jennifer; Kang, Hyun Min; Stambolian, Dwight; Chew, Emily Y.; Branham, Kari E.; Heckenlively, John; Fulton, Robert; Wilson, Richard K.; Mardis, Elaine R.; Lin, Xihong; Swaroop, Anand; Zöllner, Sebastian; Abecasis, Gonçalo R.

    2014-01-01

    Knowledge of individual ancestry is important for genetic association studies where population structure leads to false positive signals. Estimating individual ancestry with targeted sequence data, which constitutes the bulk of current sequence datasets, is challenging. Here, we propose a new method for accurate estimation of genetic ancestry. Our method skips genotype calling and directly analyzes sequence reads. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry with whole genome shotgun coverage as low as 0.001X. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1X. At an even finer-scale, the method improves discrimination between exome-sequenced participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and reduce the risk of spurious findings due to population structure. PMID:24633160

  3. Palate Shape and Depth: A Shape-Matching and Machine Learning Method for Estimating Ancestry from Human Skeletal Remains.

    PubMed

    Maier, Christopher A; Zhang, Kang; Manhein, Mary H; Li, Xin

    2015-09-01

    In the past, assessing ancestry relied on the naked eye and observer experience; however, replicability has become an important aspect of such analysis through the application of metric techniques. This study examines palate shape and assesses ancestry quantitatively using a 3D digitizer and shape-matching and machine learning methods. Palate curves and depths were recorded, processed, and tested for 376 individuals. Palate shape was an accurate indicator of ancestry in 58% of cases. Cluster analysis revealed that the parabolic, hyperbolic, and elliptical shapes are discrete from one another. Preliminary results indicate that palate depth in Hispanic individuals is greatest. Palate shape appears to be a useful indicator of ancestry, particularly when assessed by a computer. However, these data suggest that palate shape is not useful for assessing ancestry in Hispanic individuals. Although ancestry may be determined from palate shape, the use of multiple features is recommended and more reliable.

  4. Individual- and Area-level Unemployment Influence Smoking Cessation Among African Americans Participating in a Randomized Clinical Trial

    PubMed Central

    Kendzor, Darla E.; Reitzel, Lorraine R.; Mazas, Carlos A.; Cofta-Woerpel, Ludmila M.; Cao, Yumei; Ji, Lingyun; Costello, Tracy J.; Vidrine, Jennifer Irvin; Businelle, Michael S.; Li, Yisheng; Castro, Yessenia; Ahluwalia, Jasjit S.; Cinciripini, Paul M.; Wetter, David W.

    2012-01-01

    African Americans suffer disproportionately from the adverse health consequences of smoking, and also report substantially lower socioeconomic status than Whites and other racial/ethnic groups in the U.S. Although socioeconomic disadvantage is known to have a negative influence on smoking cessation rates and overall health, little is known about the influence of socioeconomic status on smoking cessation specifically among African Americans. Thus, the purpose of the current study was to characterize the impact of several individual- and area-level indicators of socioeconomic status on smoking cessation among African Americans. Data were collected as part of a smoking cessation intervention study for African American smokers (N = 379) recruited from the Houston, Texas, metropolitan area, who participated in the study between 2005 and 2007. The separate and combined influences of individual-level (insurance status, unemployment, education, and income) and area-level (neighborhood unemployment, education, income, and poverty) indicators of socioeconomic status on continuous smoking abstinence were examined across time intervals using continuation ratio logit modeling. Individual-level analyses indicated that unemployment was significantly associated with reduced odds of smoking abstinence, while higher income was associated with greater odds of abstinence. However, only unemployment remained a significant predictor of abstinence when unemployment and income were included in the model together. Area-level analyses indicated that greater neighborhood unemployment and poverty were associated with reduced odds of smoking abstinence, while greater neighborhood education was associated with higher odds of abstinence. However, only neighborhood unemployment remained significantly associated with abstinence status when individual-level income and unemployment were included in the model. Overall, findings suggest that individual- and area-level unemployment have a negative

  5. A rapid screening of ancestry for genetic association studies in an admixed population from Pernambuco, Brazil.

    PubMed

    Coelho, A V C; Moura, R R; Cavalcanti, C A J; Guimarães, R L; Sandrin-Garcia, P; Crovella, S; Brandão, L A C

    2015-03-31

    Genetic association studies determine how genes influence traits. However, non-detected population substructure may bias the analysis, resulting in spurious results. One method to detect substructure is to genotype ancestry informative markers (AIMs) besides the candidate variants, quantifying how much ancestral populations contribute to the samples' genetic background. The present study aimed to use a minimum quantity of markers, while retaining full potential to estimate ancestries. We tested the feasibility of a subset of the 12 most informative markers from a previously established study to estimate influence from three ancestral populations: European, African and Amerindian. The results showed that in a sample with a diverse ethnicity (N = 822) derived from 1000 Genomes database, the 12 AIMs had the same capacity to estimate ancestries when compared to the original set of 128 AIMs, since estimates from the two panels were closely correlated. Thus, these 12 SNPs were used to estimate ancestry in a new sample (N = 192) from an admixed population in Recife, Northeast Brazil. The ancestry estimates from Recife subjects were in accordance with previous studies, showing that Northeastern Brazilian populations show great influence from European ancestry (59.7%), followed by African (23.0%) and Amerindian (17.3%) ancestries. Ethnicity self-classification according to skin-color was confirmed to be a poor indicator of population substructure in Brazilians, since ancestry estimates overlapped between classifications. Thus, our streamlined panel of 12 markers may substitute panels with more markers, while retaining the capacity to control for population substructure and admixture, thereby reducing sample processing time.

  6. African Americans and Mathematics Outcomes on National Assessment of Educational Progress: Parental and Individual Influences

    ERIC Educational Resources Information Center

    Noble, Richard, III; Morton, Crystal Hill

    2013-01-01

    This study investigated within group differences between African American female and male students who participated in the 2009 National Assessment of Educational Progress mathematics assessment. Using results from participating states, we compare average scale scores of African American students based on home regulatory environment and interest…

  7. Worldwide Patterns of Ancestry, Divergence, and Admixture in Domesticated Cattle

    PubMed Central

    Decker, Jared E.; McKay, Stephanie D.; Rolf, Megan M.; Kim, JaeWoo; Molina Alcalá, Antonio; Sonstegard, Tad S.; Hanotte, Olivier; Götherström, Anders; Seabury, Christopher M.; Praharani, Lisa; Babar, Masroor Ellahi; Correia de Almeida Regitano, Luciana; Yildiz, Mehmet Ali; Heaton, Michael P.; Liu, Wan-Sheng; Lei, Chu-Zhao; Reecy, James M.; Saif-Ur-Rehman, Muhammad; Schnabel, Robert D.; Taylor, Jeremy F.

    2014-01-01

    The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds and populations have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 animals, we evaluate the population structure of 134 domesticated bovid breeds. Regardless of the analytical method or sample subset, the three major groups of Asian indicine, Eurasian taurine, and African taurine were consistently observed. Patterns of geographic dispersal resulting from co-migration with humans and exportation are recognizable in phylogenetic networks. All analytical methods reveal patterns of hybridization which occurred after divergence. Using 19 breeds, we map the cline of indicine introgression into Africa. We infer that African taurine possess a large portion of wild African auroch ancestry, causing their divergence from Eurasian taurine. We detect exportation patterns in Asia and identify a cline of Eurasian taurine/indicine hybridization in Asia. We also identify the influence of species other than Bos taurus taurus and B. t. indicus in the formation of Asian breeds. We detect the pronounced influence of Shorthorn cattle in the formation of European breeds. Iberian and Italian cattle possess introgression from African taurine. American Criollo cattle originate from Iberia, and not directly from Africa with African ancestry inherited via Iberian ancestors. Indicine introgression into American cattle occurred in the Americas, and not Europe. We argue that cattle migration, movement and trading followed by admixture have been important forces in shaping modern bovine genomic variation. PMID:24675901

  8. Associations Between Individual and Family Level Characteristics and Parenting Practices in Incarcerated African American Fathers

    PubMed Central

    Wilson, Melvin N.

    2009-01-01

    We investigated the reported parenting practices of fifty incarcerated African American fathers. Fathers were interviewed using hypothetical vignettes adapted from the Parenting Dimensions Inventory (PDI) and received scores on two parenting practices: responsive and restrictive. Father's individual level (education and length of time spent incarcerated) and family level (number of relationships that have borne children) characteristics were significantly associated with their parenting practices. Based on canonical correlation analysis, on function one, responsive parenting was positively associated with education level and negatively associated with both cumulative incarceration time and more numerous partner fertility. Restrictive parenting was negatively associated with education level and positively associated with both cumulative incarceration time and more numerous partner fertility. Function 2 capitalized on variance in the restrictive parenting predictor that was not utilized in function 1, and likely captured lack of opportunity to parent. On function 2, restrictive parenting was negatively associated with cumulative time spent incarcerated and more numerous partner fertility. In all, results suggest that prison-based education programs should be part of an overall response to incarcerated fathers. These results add to the growing body of research on incarcerated fathers and fragile families. PMID:19802371

  9. Individual interviews with African-American women regarding condom use: a pilot study.

    PubMed

    Hunter, Teressa Sanders

    2010-07-01

    African-American women between 25 and 34 years of age are disproportionately affected by HIV/AIDS. Current prevention techniques, including education, have not had a significant influence on decreasing the rates of HIV and increasing safer sexual practices among some African-American women. This pilot study is one step towards increasing the understanding of this serious problem and developing effective interventions to stem the tide of HIV infection in African-American women. A grounded theory approach was used to address the process that unmarried, heterosexual, African-American women used to negotiate condom use with their sexual partner. Major concepts, connections between the categories, and theoretical codes are identified in this study and can be used to predict, speculate, explain, and understand the reported behavior of African-American women in negotiating condom use with their sexual partner.

  10. Complex Ancient Genetic Structure and Cultural Transitions in Southern African Populations

    PubMed Central

    Montinaro, Francesco; Busby, George B. J.; Gonzalez-Santos, Miguel; Oosthuitzen, Ockie; Oosthuitzen, Erika; Anagnostou, Paolo; Destro-Bisol, Giovanni; Pascali, Vincenzo L.; Capelli, Cristian

    2017-01-01

    The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries. PMID:27838627

  11. Palenque de San Basilio in Colombia: genetic data support an oral history of a paternal ancestry in Congo.

    PubMed

    Ansari-Pour, Naser; Moñino, Yves; Duque, Constanza; Gallego, Natalia; Bedoya, Gabriel; Thomas, Mark G; Bradman, Neil

    2016-03-30

    The Palenque, a black community in rural Colombia, have an oral history of fugitive African slaves founding a free village near Cartagena in the seventeenth century. Recently, linguists have identified some 200 words in regular use that originate in a Kikongo language, with Yombe, mainly spoken in the Congo region, being the most likely source. The non-recombining portion of the Y chromosome (NRY) and mitochondrial DNA were analysed to establish whether there was greater similarity between present-day members of the Palenque and Yombe than between the Palenque and 42 other African groups (for all individuals,n= 2799) from which forced slaves might have been taken. NRY data are consistent with the linguistic evidence that Yombe is the most likely group from which the original male settlers of Palenque came. Mitochondrial DNA data suggested substantial maternal sub-Saharan African ancestry and a strong founder effect but did not associate Palenque with any particular African group. In addition, based on cultural data including inhabitants' claims of linguistic differences, it has been hypothesized that the two districts of the village (Abajo and Arriba) have different origins, with Arriba founded by men originating in Congo and Abajo by those born in Colombia. Although significant genetic structuring distinguished the two from each other, no supporting evidence for this hypothesis was found.

  12. Palenque de San Basilio in Colombia: genetic data support an oral history of a paternal ancestry in Congo

    PubMed Central

    Ansari-Pour, Naser; Moñino, Yves; Duque, Constanza; Gallego, Natalia; Bedoya, Gabriel; Thomas, Mark G.; Bradman, Neil

    2016-01-01

    The Palenque, a black community in rural Colombia, have an oral history of fugitive African slaves founding a free village near Cartagena in the seventeenth century. Recently, linguists have identified some 200 words in regular use that originate in a Kikongo language, with Yombe, mainly spoken in the Congo region, being the most likely source. The non-recombining portion of the Y chromosome (NRY) and mitochondrial DNA were analysed to establish whether there was greater similarity between present-day members of the Palenque and Yombe than between the Palenque and 42 other African groups (for all individuals, n = 2799) from which forced slaves might have been taken. NRY data are consistent with the linguistic evidence that Yombe is the most likely group from which the original male settlers of Palenque came. Mitochondrial DNA data suggested substantial maternal sub-Saharan African ancestry and a strong founder effect but did not associate Palenque with any particular African group. In addition, based on cultural data including inhabitants' claims of linguistic differences, it has been hypothesized that the two districts of the village (Abajo and Arriba) have different origins, with Arriba founded by men originating in Congo and Abajo by those born in Colombia. Although significant genetic structuring distinguished the two from each other, no supporting evidence for this hypothesis was found. PMID:27030413

  13. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.

    PubMed

    Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K; Thomas, Venetta; Ambrosone, Christine B; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J; Cheng, Iona; Chu, Lisa; Deming, Sandra L; Driver, W Ryan; Goodman, Phyllis; Hayes, Richard B; Hennis, Anselm J M; Hsing, Ann W; Hu, Jennifer J; Ingles, Sue A; John, Esther M; Kittles, Rick A; Kolb, Suzanne; Leske, M Cristina; Millikan, Robert C; Monroe, Kristine R; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Ben A; Schumacher, Fredrick; Stanford, Janet L; Signorello, Lisa B; Strom, Sara S; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G; Stram, Alexander H; Kolonel, Laurence N; Le Marchand, Loïc; Henderson, Brian E; Haiman, Christopher A; Stram, Daniel O

    2015-01-01

    Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability

  14. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults

    PubMed Central

    Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K.; Thomas, Venetta; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J.; Cheng, Iona; Chu, Lisa; Deming, Sandra L.; Driver, W. Ryan; Goodman, Phyllis; Hayes, Richard B.; Hennis, Anselm J. M.; Hsing, Ann W.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Kittles, Rick A.; Kolb, Suzanne; Leske, M. Cristina; Monroe, Kristine R.; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Ben A.; Schumacher, Fredrick; Stanford, Janet L.; Signorello, Lisa B.; Strom, Sara S.; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S.; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G.; Stram, Alexander H.; Kolonel, Laurence N.; Marchand, Loïc Le; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

    2015-01-01

    Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability

  15. A Quasi-Exclusive European Ancestry in the Senepol Tropical Cattle Breed Highlights the Importance of the slick Locus in Tropical Adaptation

    PubMed Central

    Flori, Laurence; Gonzatti, Mary Isabel; Thevenon, Sophie; Chantal, Isabelle; Pinto, Joar; Berthier, David; Aso, Pedro M.; Gautier, Mathieu

    2012-01-01

    Background The Senepol cattle breed (SEN) was created in the early XXth century from a presumed cross between a European (EUT) breed (Red Poll) and a West African taurine (AFT) breed (N’Dama). Well adapted to tropical conditions, it is also believed trypanotolerant according to its putative AFT ancestry. However, such origins needed to be verified to define relevant husbandry practices and the genetic background underlying such adaptation needed to be characterized. Methodology/Principal Findings We genotyped 153 SEN individuals on 47,365 SNPs and combined the resulting data with those available on 18 other populations representative of EUT, AFT and Zebu (ZEB) cattle. We found on average 89% EUT, 10.4% ZEB and 0.6% AFT ancestries in the SEN genome. We further looked for footprints of recent selection using standard tests based on the extent of haplotype homozygosity. We underlined i) three footprints on chromosome (BTA) 01, two of which are within or close to the polled locus underlying the absence of horns and ii) one footprint on BTA20 within the slick hair coat locus, involved in thermotolerance. Annotation of these regions allowed us to propose three candidate genes to explain the observed signals (TIAM1, GRIK1 and RAI14). Conclusions/Significance Our results do not support the accepted concept about the AFT origin of SEN breed. Initial AFT ancestry (if any) might have been counter-selected in early generations due to breeding objectives oriented in particular toward meat production and hornless phenotype. Therefore, SEN animals are likely susceptible to African trypanosomes which questions the importation of SEN within the West African tsetse belt, as promoted by some breeding societies. Besides, our results revealed that SEN breed is predominantly a EUT breed well adapted to tropical conditions and confirmed the importance in thermotolerance of the slick locus. PMID:22675421

  16. Genetically Determined Amerindian Ancestry Correlates with Increased Frequency of Risk Alleles for Systemic Lupus Erythematosus

    PubMed Central

    Sanchez, E; Webb, R; Rasmussen, A.; Kelly, J.A; Riba, L.; Kaufman, K.M.; Garcia-de la Torre, I.; Moctezuma, J.F.; Maradiaga-Ceceña, M.A.; Cardiel, M.; Acevedo, E.; Cucho-Venegas, M.; Garcia, M.A.; Gamron, S.; Pons-Estel, B.A.; Vasconcelos, C.; Martin, J.; Tusié-Luna, T.; Harley, J.B.; Richardson, B.; Sawalha, A.H.; Alarcón-Riquelme, M.E.

    2011-01-01

    Objectives To analyze if genetically determined Amerindian ancestry predicts the increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus. Methods Single nucleotide polymorphisms within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo normal healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation of the presence of risk alleles with ancestry was done using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, PDCD1, ITGAM, and IRF5 were associated with lupus in a Hispanic-Mestizo cohort enriched for European and Amerindian ancestry. In addition, two SNPs within the MHC region, previously associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression we predict an average increase of 2.34 risk alleles when comparing a lupus patient with 100% Amerindian ancestry to an SLE patient with 0% American Indian Ancestry (p<0.0001). SLE patients with 43% more Amerindian ancestry are predicted to carry one additional risk allele. Conclusion Amerindian ancestry increased the number of risk alleles for lupus. PMID:20848568

  17. Association of serum lipid components and obesity with genetic ancestry in an admixed population of elderly women

    PubMed Central

    Lins, Tulio C.; Pires, Alause S.; Paula, Roberta S.; Moraes, Clayton F.; Vieira, Rodrigo G.; Vianna, Lucy G.; Nobrega, Otávio T.; Pereira, Rinaldo W.

    2012-01-01

    The prevalence of metabolic disorders varies among ethnic populations and these disorders represent a critical health care issue for elderly women. This study investigated the correlation between genetic ancestry and body composition, metabolic traits and clinical status in a sample of elderly women. Clinical, nutritional and anthropometric data were collected from 176 volunteers. Genetic ancestry was estimated using 23 ancestry-informative markers. Pearsons correlation test was used to examine the relationship between continuous variables and an independent samples t-test was used to compare the means of continuous traits within categorical variables. Overall ancestry was a combination of European (57.49%), Native American (25.78%) and African (16.73%). Significant correlations were found for European ancestry with body mass index (r = 0.165; p = 0.037) and obesity (mean difference (MD) = 5.3%; p = 0.042). African ancestry showed a significant correlation with LDL (r = 0.159, p = 0.035), VLDL (r = −0.185; p = 0.014), hypertriglyceridemia (MD = 6.4%; p = 0.003) and hyperlipidemia (MD = 4.8%; p = 0.026). Amerindian ancestry showed a significant correlation with triglyceride levels (r = 0.150; p = 0.047) and hypertriglyceridemia (MD = 4.5%; p = 0.039). These findings suggest that genetic admixture may influence the etiology of lipid metabolism-related diseases and obesity in elderly women. PMID:23055794

  18. Inferring Genetic Ancestry: Opportunities, Challenges, and Implications

    PubMed Central

    Royal, Charmaine D.; Novembre, John; Fullerton, Stephanie M.; Goldstein, David B.; Long, Jeffrey C.; Bamshad, Michael J.; Clark, Andrew G.

    2010-01-01

    Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of “ancestry” is subject to misunderstanding in both the general and scientific communities. What do we mean by ancestry? How exactly is ancestry measured? How far back can such ancestry be defined and by which genetic tools? How do we validate inferences about ancestry in genetic research? What are the data that demonstrate our ability to do this correctly? What can we say and what can we not say from our research findings and the test results that we generate? This white paper from the American Society of Human Genetics (ASHG) Ancestry and Ancestry Testing Task Force builds upon the 2008 ASHG Ancestry Testing Summary Statement in providing a more in-depth analysis of key scientific and non-scientific aspects of genetic ancestry inference in academia and industry. It culminates with recommendations for advancing the current debate and facilitating the development of scientifically based, ethically sound, and socially attentive guidelines concerning the use of these continually evolving technologies. PMID:20466090

  19. The genomic landscape of Neanderthal ancestry in present-day humans.

    PubMed

    Sankararaman, Sriram; Mallick, Swapan; Dannemann, Michael; Prüfer, Kay; Kelso, Janet; Pääbo, Svante; Patterson, Nick; Reich, David

    2014-03-20

    Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

  20. Regional differences in awareness and attitudes regarding genetic testing for disease risk and ancestry.

    PubMed

    Jonassaint, Charles R; Santos, Eunice R; Glover, Crystal M; Payne, Perry W; Fasaye, Grace-Ann; Oji-Njideka, Nefertiti; Hooker, Stanley; Hernandez, Wenndy; Foster, Morris W; Kittles, Rick A; Royal, Charmaine D

    2010-09-01

    Little is known about the lay public's awareness and attitudes concerning genetic testing and what factors influence their perspectives. The existing literature focuses mainly on ethnic and socioeconomic differences; however, here we focus on how awareness and attitudes regarding genetic testing differ by geographical regions in the US. We compared awareness and attitudes concerning genetic testing for disease risk and ancestry among 452 adults (41% Black and 67% female) in four major US cities, Norman, OK; Cincinnati, OH; Harlem, NY; and Washington, DC; prior to their participation in genetic ancestry testing. The OK participants reported more detail about their personal ancestries (p = 0.02) and valued ancestry testing over disease testing more than all other sites (p < 0.01). The NY participants were more likely than other sites to seek genetic testing for disease (p = 0.01) and to see benefit in finding out more about one's ancestry (p = 0.02), while the DC participants reported reading and hearing more about genetic testing for African ancestry than all other sites (p < 0.01). These site differences were not better accounted for by sex, age, education, self-reported ethnicity, religion, or previous experience with genetic testing/counseling. Regional differences in awareness and attitudes transcend traditional demographic predictors, such as ethnicity, age and education. Local sociocultural factors, more than ethnicity and socioeconomic status, may influence the public's awareness and belief systems, particularly with respect to genetics.

  1. Associations among ancestry, geography and breast cancer incidence, mortality, and survival in Trinidad and Tobago

    PubMed Central

    Warner, Wayne A; Morrison, Robert L; Lee, Tammy Y; Williams, Tanisha M; Ramnarine, Shelina; Roach, Veronica; Slovacek, Simeon; Maharaj, Ravi; Bascombe, Nigel; Bondy, Melissa L; Ellis, Matthew J; Toriola, Adetunji T; Roach, Allana; Llanos, Adana A M

    2015-01-01

    Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates (Incidence: 66.96; Mortality: 30.82 per 100,000) compared to women of East Indian (Incidence: 41.04, Mortality: 14.19 per 100,000) or mixed ancestry (Incidence: 36.72, Mortality: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT. PMID:26338451

  2. Race, genetic ancestry and response to antidepressant treatment for major depression.

    PubMed

    Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

    2013-12-01

    The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials.

  3. The African diaspora: history, adaptation and health.

    PubMed

    Rotimi, Charles N; Tekola-Ayele, Fasil; Baker, Jennifer L; Shriner, Daniel

    2016-12-01

    The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and 'Eurasian' admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities.

  4. On the Outside Looking in: An African American Family's Experience in an Individualized Education Plan Meeting

    ERIC Educational Resources Information Center

    Angelov, Azure D. S.; Anderson, Sheri L.

    2012-01-01

    The current laws that mandate special education originated through the advocacy of families (Turnbull & Turnbull, 1990). Over the years, families have challenged the system to provide free and appropriate public educations for their children. We share, through qualitative measures, the experiences of one African American family and the…

  5. Genome-wide detection of natural selection in African Americans pre- and post-admixture.

    PubMed

    Jin, Wenfei; Xu, Shuhua; Wang, Haifeng; Yu, Yongguo; Shen, Yiping; Wu, Bailin; Jin, Li

    2012-03-01

    It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre- and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre- and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs.

  6. Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries

    PubMed Central

    Baurley, James W.; Edlund, Christopher K.; Pardamean, Carissa I.; Conti, David V.; Krasnow, Ruth; Javitz, Harold S.; Hops, Hyman; Swan, Gary E.; Benowitz, Neal L.

    2016-01-01

    Introduction: Metabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3′-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed. Methods: Three hundred twelve individuals of self-identified European, African, and Asian American ancestry were genotyped and included in ancestry-specific genome-wide association scans (GWAS) and a meta-GWAS analysis of the NMR. We modeled natural-log transformed NMR with covariates: principal components of genetic ancestry, age, sex, body mass index, and smoking status. Results: African and Asian American NMRs were statistically significantly (P values ≤ 5E-5) lower than European American NMRs. Meta-GWAS analysis identified 36 genome-wide significant variants over a 43 kilobase pair region at CYP2A6 with minimum P = 2.46E-18 at rs12459249, proximal to CYP2A6. Additional minima were located in intron 4 (rs56113850, P = 6.61E-18) and in the CYP2A6-CYP2A7 intergenic region (rs34226463, P = 1.45E-12). Most (34/36) genome-wide significant variants suggested reduced CYP2A6 activity; functional mechanisms were identified and tested in knowledge-bases. Conditional analysis resulted in intergenic variants of possible interest (P values < 5E-5). Conclusions: This meta-GWAS of the NMR identifies CYP2A6 variants, replicates the top-ranked single nucleotide polymorphism from a recent Finnish meta-GWAS of the NMR, identifies functional mechanisms, and provides pan

  7. Quantification of Maxillary Dental Arcade Curvature and the Estimation of Biological Ancestry in Forensic Anthropology.

    PubMed

    Clark, Melissa A; Guatelli-Steinberg, Debbie; Hubbe, Mark; Stout, Sam

    2016-01-01

    Previous studies suggest that palate shape is a useful indicator of biological ancestry in human remains. This study evaluates interobserver error in ancestry estimation using palate shape and explores palate shape variation in Gullah (descendants of West Africans) and Seminole (Indigenous American) population samples using geometric morphometric analysis. Ten participants were asked to ascribe biological ancestry and shape to 28 dental casts based on a classification scheme employed in previous studies. The mean correct classification was 42.0%, indicating that the likelihood of assigning the correct ancestry is very poor and not significantly different from random assignment (p = 0.12). The accuracy analysis based on categorical classification of the casts was complemented by geometric morphometric analysis of nine 3D landmarks reflecting palate shape of 158 casts. Principal component analysis results show no difference between populations regarding palate shape, and cross-validated discriminant function analysis correctly classified only 62.0% of the specimens. Combined, these results show that previous methods to estimate ancestry are inaccurate and that this inaccuracy is probably due to a lack of palate shape differences between groups, rather than limitation of the analytical method per se. Therefore, we recommend caution should be used when choosing to apply the analysis of palate shape in forensically relevant contexts.

  8. Maximum-likelihood estimation of recent shared ancestry (ERSA)

    PubMed Central

    Huff, Chad D.; Witherspoon, David J.; Simonson, Tatum S.; Xing, Jinchuan; Watkins, W. Scott; Zhang, Yuhua; Tuohy, Therese M.; Neklason, Deborah W.; Burt, Randall W.; Guthery, Stephen L.; Woodward, Scott R.; Jorde, Lynn B.

    2011-01-01

    Accurate estimation of recent shared ancestry is important for genetics, evolution, medicine, conservation biology, and forensics. Established methods estimate kinship accurately for first-degree through third-degree relatives. We demonstrate that chromosomal segments shared by two individuals due to identity by descent (IBD) provide much additional information about shared ancestry. We developed a maximum-likelihood method for the estimation of recent shared ancestry (ERSA) from the number and lengths of IBD segments derived from high-density SNP or whole-genome sequence data. We used ERSA to estimate relationships from SNP genotypes in 169 individuals from three large, well-defined human pedigrees. ERSA is accurate to within one degree of relationship for 97% of first-degree through fifth-degree relatives and 80% of sixth-degree and seventh-degree relatives. We demonstrate that ERSA's statistical power approaches the maximum theoretical limit imposed by the fact that distant relatives frequently share no DNA through a common ancestor. ERSA greatly expands the range of relationships that can be estimated from genetic data and is implemented in a freely available software package. PMID:21324875

  9. European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

    PubMed Central

    Santos, Antônio Carlos; Lana-Peixoto, Marco Aurélio; Rocha, Cristiane Franklin; Brito, Maria Lucia; de Oliveira, Enedina Maria Lobato; Bichuetti, Denis Bernardi; Gabbai, Alberto Alan; Diniz, Denise Sisterolli; Kaimen-Maciel, Damacio Ramon; Comini-Frota, Elizabeth Regina; Vieira Wiezel, Claudia E.; Muniz, Yara Costa Netto; da Silva Costa, Roberta Martins; Mendes-Junior, Celso Teixeira; Donadi, Eduardo Antônio; Barreira, Amilton Antunes; Simões, Aguinaldo Luiz

    2013-01-01

    Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. PMID:23527051

  10. Multi-InDel Analysis for Ancestry Inference of Sub-Populations in China

    PubMed Central

    Sun, Kuan; Ye, Yi; Luo, Tao; Hou, Yiping

    2016-01-01

    Ancestry inference is of great interest in diverse areas of scientific researches, including the forensic biology, medical genetics and anthropology. Various methods have been published for distinguishing populations. However, few reports refer to sub-populations (like ethnic groups) within Asian populations for the limitation of markers. Several InDel loci located very tightly in physical positions were treated as one marker by us, which is multi-InDel. The multi-InDel shows potential as Ancestry Inference Marker (AIM). In this study, we performed a genome-wide scan for multi-InDels as AIM. After examining the FST distributions in the 1000 Genomes Database, 12 candidates were selected and validated for eastern Asian populations. A multiplexed assay was developed as a panel to genotype 12 multi-InDel markers simultaneously. Ancestry component analysis with STRUCTURE and principal component analysis (PCA) were employed to estimate its capability for ancestry inference. Furthermore, ancestry assignments of trial individuals were conducted. It proved to be very effective when 210 samples from Han and Tibetan individuals in China were tested. The panel consisting of multi-InDel markers exhibited considerable potency in ancestry inference, and was suggested to be applied in forensic practices and genetic population studies. PMID:28004788

  11. Enhancing the Number of African Americans Who Pursue STEM PhDs: Meyerhoff Scholarship Program Outcomes, Processes, and Individual Predictors

    PubMed Central

    Maton, Kenneth I.; Sto Domingo, Mariano R.; Stolle-McAllister, Kathleen E.; Zimmerman, J. Lynn; Hrabowski, Freeman A.

    2011-01-01

    The current study examines the outcomes, processes, and individual predictors of pursuit of a STEM PhD among African-American students in the Meyerhoff Scholarship Program. Meyerhoff students were nearly five times more likely than comparison students to pursue a STEM PhD. Program components consistently rated as important were financial scholarship, being part of the Meyerhoff Program community, the Summer Bridge program, study groups, staff academic advising, and summer research opportunities. Furthermore, focus group findings revealed student internalization of key Meyerhoff Program values, including a commitment to excellence, accountability, group success, and giving back. In terms of individual predictors, multinomial logit regression analyses revealed that Meyerhoff students with higher levels of research excitement at college entry were more likely to pursue a STEM PhD. PMID:21841904

  12. Descriptive analysis of individual and community factors among African American youths in urban public housing.

    PubMed

    Nebbitt, Von E; Williams, James Herbert; Lombe, Margaret; McCoy, Henrika; Stephens, Jennifer

    2014-07-01

    African American adolescents are disproportionately represented in urban public housing developments. These neighborhoods are generally characterized by high rates of poverty, crime, violence, and disorganization. Although evidence is emerging on youths in these communities, little is known about their depressive symptoms, perceived efficacy, or frequency of substance use and sex-risk behavior. Further, even less is known about their exposure to community and household violence, their parents' behavior, or their sense of connection to their communities. Using a sample of 782 African American adolescents living in public housing neighborhoods located in four large U.S. cities, this article attempts to rectify the observed gap in knowledge by presenting a descriptive overview of their self-reported depressive symptoms; self-efficacy; frequencies of delinquent and sexual-risk behavior; and alcohol, tobacco, and other drug use. The self-reported ratings of their parents' behavior as well as their exposure to community and household violence are presented. Analytic procedures include descriptive statistics and mean comparisons between genders and across research cities. Results suggest several differences between genders and across research sites. However, results are not very different from national data. Implications for social work practice are discussed.

  13. Women of African Descent: Persistence in Completing Doctorates

    ERIC Educational Resources Information Center

    Iddrisu, Vannetta Bailey

    2010-01-01

    This study examines the educational persistence of women of African descent (WOAD) in pursuit of a doctorate degree at universities in the southeastern United States. WOAD are women of African ancestry born outside the African continent. These women are heirs to an inner dogged determination and spirit to survive despite all odds (Pulliam, 2003,…

  14. Estimating ancestry and heterozygosity of hybrids using molecular markers

    PubMed Central

    2012-01-01

    Background Hybridization, genetic mixture of distinct populations, gives rise to myriad recombinant genotypes. Characterizing the genomic composition of hybrids is critical for studies of hybrid zone dynamics, inheritance of traits, and consequences of hybridization for evolution and conservation. Hybrid genomes are often summarized either by an estimate of the proportion of alleles coming from each ancestral population or classification into discrete categories like F1, F2, backcross, or merely “hybrid” vs. “pure”. In most cases, it is not realistic to classify individuals into the restricted set of classes produced in the first two generations of admixture. However, the continuous ancestry index misses an important dimension of the genotype. Joint consideration of ancestry together with interclass heterozygosity (proportion of loci with alleles from both ancestral populations) captures all of the information in the discrete classification without the unrealistic assumption that only two generations of admixture have transpired. Methods I describe a maximum likelihood method for joint estimation of ancestry and interclass heterozygosity. I present two worked examples illustrating the value of the approach for describing variation among hybrid populations and evaluating the validity of the assumption underlying discrete classification. Results Naively classifying natural hybrids into the standard six line cross categories can be misleading, and false classification can be a serious problem for datasets with few molecular markers. My analysis underscores previous work showing that many (50 or more) ancestry informative markers are needed to avoid erroneous classification. Conclusion Although classification of hybrids might often be misleading, valuable inferences can be obtained by focusing directly on distributions of ancestry and heterozygosity. Estimating and visualizing the joint distribution of ancestry and interclass heterozygosity is an effective way

  15. Mixing state of aerosols and direct observation of carbonaceous and marine coatings on African dust by individual particle analysis

    NASA Astrophysics Data System (ADS)

    Deboudt, Karine; Flament, Pascal; ChoëL, Marie; Gloter, Alexandre; Sobanska, Sophie; Colliex, Christian

    2010-12-01

    The mixing state of aerosols collected at M'Bour, Senegal, during the Special Observing Period conducted in January-February 2006 (SOP-0) of the African Monsoon Multidisciplinary Analysis project (AMMA), was studied by individual particle analysis. The sampling location on the Atlantic coast is particularly adapted for studying the mixing state of tropospheric aerosols since it is (1) located on the path of Saharan dust plumes transported westward over the northern tropical Atlantic, (2) influenced by biomass burning events particularly frequent from December to March, and (3) strongly influenced by anthropogenic emissions from polluted African cities. Particle size, morphology, and chemical composition were determined for 12,672 particles using scanning electron microscopy (automated SEM-EDX). Complementary analyses were performed using transmission electron microscopy combined with electron energy loss spectrometry (TEM-EELS) and Raman microspectrometry. Mineral dust and carbonaceous and marine compounds were predominantly found externally mixed, i.e., not present together in the same particles. Binary internally mixed particles, i.e., dust/carbonaceous, carbonaceous/marine, and dust/marine mixtures, accounted for a significant fraction of analyzed particles (from 10.5% to 46.5%). Western Sahara was identified as the main source of mineral dust. Two major types of carbonaceous particles were identified: "tar balls" probably coming from biomass burning emissions and soot from anthropogenic emissions. Regarding binary internally mixed particles, marine and carbonaceous compounds generally formed a coating on mineral dust particles. The carbonaceous coating observed at the particle scale on African dust was evidenced by the combined use of elemental and molecular microanalysis techniques, with the identification of an amorphous rather than crystallized carbon structure.

  16. Predictors of Co-Occurring Risk Behavior Trajectories among Economically Disadvantaged African American Youth: Contextual and Individual Factors

    PubMed Central

    Sterrett, Emma M.; Dymnicki, Allison B.; Henry, David; Byck, Gayle; Bolland, John; Mustanski, Brian

    2014-01-01

    Purpose African American youth, particularly those from low-income backgrounds, evidence high rates of negative outcomes associated with three problem behaviors, conduct problems, risky sexual behavior, and substance use. This study used a contextually-tailored version of Problem Behavior Theory (PBT) to examine predictors of the simultaneous development of problem behaviors in this specific cultural group. Methods Socio-contextual and individual variables representing four PBT predictor categories, controls protection, support protection, models risk, and vulnerability risk, were examined as predictors of co-occurring problem behaviors among economically disadvantaged African American adolescents (n = 949). Specifically, the likelihood of following three classes of multiple problem behavior trajectories spanning ages 12 to 18, labeled the “early experimenters,” “increasing high risk-takers,” and “adolescent-limited” classes, as opposed to a “normative” class was examined. Results Among other findings, controls protection in the form of a more stringent household curfew at age 12 was related to a lower likelihood of being in the “early experimenters” and “increasing high risk-takers” classes. Conversely, vulnerability risk manifested as stronger attitudes of violence inevitability was associated with a higher likelihood of being in the “early experimenters” class. However, the PBT category of support protection was not associated with risk trajectory class. More distal neighborhood-level manifestations of PBT categories also did not predict co-occurring behavior problems. Conclusion Guided by an incorporation of contextually-salient processes into PBT, prevention programs aiming to decrease co-occurring problem behaviors among low-income African American adolescents would do well to target both proximal systems and psychological constructs related to perceived security throughout adolescence. PMID:24755141

  17. Displacement of the Lamina Cribrosa in Response to Acute Intraocular Pressure Elevation in Normal Individuals of African and European Descent

    PubMed Central

    Fazio, Massimo A.; Johnstone, John K.; Smith, Brandon; Wang, Lan; Girkin, Christopher A.

    2016-01-01

    Purpose To assess if the in vivo mechanical displacement of the anterior laminar cribrosa surface (ALCS) as a response of an acute elevation in intraocular pressure (IOP) differs in individuals of European (ED) and African descent (AD). Methods Spectral-domain optical coherence tomography (SDOCT) scans were obtained from 24 eyes of 12 individuals of AD and 18 eyes of 9 individuals of ED at their normal baseline IOP and after 60 seconds IOP elevation using ophthalmodynamometry. Change in depth (displacement) of the LC and to the prelaminar tissue (PLT) were computed in association with the change (delta) in IOP (Δ IOP), race, age, corneal thickness, corneal rigidity (ocular response analyzer [ORA]), and axial. Results In the ED group for small IOP elevations (Δ IOP < 12 mm Hg), the ALCS initially displaced posteriorly but for larger increase of IOP an anterior displacement of the lamina followed. Inversely, in the AD group the ALCS did not show a significant posterior displacement for small Δ IOP, while for larger IOP increases the ALCS significantly displaced posteriorly. Posterior displacement of the lamina cribrosa (LC) was also significantly correlated with longer axial length, higher corneal thickness, and ORA parameters. Prelaminar tissue posteriorly displaced for any magnitude of Δ IOP, in both groups. Conclusions The African descent group demonstrated a greater acute posterior bowing of the LC after adjustment for age, axial length, Bruch's membrane opening (BMO) area, and ORA parameters. Greater PLT posterior displacement was also seen in the AD group with increasing IOP, which was tightly correlated with the displacement of the LC. PMID:27367500

  18. New World cattle show ancestry from multiple independent domestication events

    PubMed Central

    McTavish, Emily Jane; Decker, Jared E.; Schnabel, Robert D.; Taylor, Jeremy F.; Hillis, David M.

    2013-01-01

    Previous archeological and genetic research has shown that modern cattle breeds are descended from multiple independent domestication events of the wild aurochs (Bos primigenius) ∼10,000 y ago. Two primary areas of domestication in the Middle East/Europe and the Indian subcontinent resulted in taurine and indicine lines of cattle, respectively. American descendants of cattle brought by European explorers to the New World beginning in 1493 generally have been considered to belong to the taurine lineage. Our analyses of 47,506 single nucleotide polymorphisms show that these New World cattle breeds, as well as many related breeds of cattle in southern Europe, actually exhibit ancestry from both the taurine and indicine lineages. In this study, we show that, although European cattle are largely descended from the taurine lineage, gene flow from African cattle (partially of indicine origin) contributed substantial genomic components to both southern European cattle breeds and their New World descendants. New World cattle breeds, such as Texas Longhorns, provide an opportunity to study global population structure and domestication in cattle. Following their introduction into the Americas in the late 1400s, semiferal herds of cattle underwent between 80 and 200 generations of predominantly natural selection, as opposed to the human-mediated artificial selection of Old World breeding programs. Our analyses of global cattle breed population history show that the hybrid ancestry of New World breeds contributed genetic variation that likely facilitated the adaptation of these breeds to a novel environment. PMID:23530234

  19. New World cattle show ancestry from multiple independent domestication events.

    PubMed

    McTavish, Emily Jane; Decker, Jared E; Schnabel, Robert D; Taylor, Jeremy F; Hillis, David M

    2013-04-09

    Previous archeological and genetic research has shown that modern cattle breeds are descended from multiple independent domestication events of the wild aurochs (Bos primigenius) ∼10,000 y ago. Two primary areas of domestication in the Middle East/Europe and the Indian subcontinent resulted in taurine and indicine lines of cattle, respectively. American descendants of cattle brought by European explorers to the New World beginning in 1493 generally have been considered to belong to the taurine lineage. Our analyses of 47,506 single nucleotide polymorphisms show that these New World cattle breeds, as well as many related breeds of cattle in southern Europe, actually exhibit ancestry from both the taurine and indicine lineages. In this study, we show that, although European cattle are largely descended from the taurine lineage, gene flow from African cattle (partially of indicine origin) contributed substantial genomic components to both southern European cattle breeds and their New World descendants. New World cattle breeds, such as Texas Longhorns, provide an opportunity to study global population structure and domestication in cattle. Following their introduction into the Americas in the late 1400s, semiferal herds of cattle underwent between 80 and 200 generations of predominantly natural selection, as opposed to the human-mediated artificial selection of Old World breeding programs. Our analyses of global cattle breed population history show that the hybrid ancestry of New World breeds contributed genetic variation that likely facilitated the adaptation of these breeds to a novel environment.

  20. Structural reconstruction of protein ancestry.

    PubMed

    Rouet, Romain; Langley, David B; Schofield, Peter; Christie, Mary; Roome, Brendan; Porebski, Benjamin T; Buckle, Ashley M; Clifton, Ben E; Jackson, Colin J; Stock, Daniela; Christ, Daniel

    2017-03-29

    Ancestral protein reconstruction allows the resurrection and characterization of ancient proteins based on computational analyses of sequences of modern-day proteins. Unfortunately, many protein families are highly divergent and not suitable for sequence-based reconstruction approaches. This limitation is exemplified by the antigen receptors of jawed vertebrates (B- and T-cell receptors), heterodimers formed by pairs of Ig domains. These receptors are believed to have evolved from an extinct homodimeric ancestor through a process of gene duplication and diversification; however molecular evidence has so far remained elusive. Here, we use a structural approach and laboratory evolution to reconstruct such molecules and characterize their interaction with antigen. High-resolution crystal structures of reconstructed homodimeric receptors in complex with hen-egg white lysozyme demonstrate how nanomolar affinity binding of asymmetrical antigen is enabled through selective recruitment and structural plasticity within the receptor-binding site. Our results provide structural evidence in support of long-held theories concerning the evolution of antigen receptors, and provide a blueprint for the experimental reconstruction of protein ancestry in the absence of phylogenetic evidence.

  1. The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day Humans.

    PubMed

    Sankararaman, Sriram; Mallick, Swapan; Patterson, Nick; Reich, David

    2016-05-09

    Some present-day humans derive up to ∼5% [1] of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals [2]. We developed methods that can disambiguate the locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry [3]. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10(-7) to 3.2 × 10(-7) for Denisovan and 2.2 × 10(-3) to 2.9 × 10(-3) for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years.

  2. A Hidden Markov Model Approach for Simultaneously Estimating Local Ancestry and Admixture Time Using Next Generation Sequence Data in Samples of Arbitrary Ploidy

    PubMed Central

    Nielsen, Rasmus

    2017-01-01

    Admixture—the mixing of genomes from divergent populations—is increasingly appreciated as a central process in evolution. To characterize and quantify patterns of admixture across the genome, a number of methods have been developed for local ancestry inference. However, existing approaches have a number of shortcomings. First, all local ancestry inference methods require some prior assumption about the expected ancestry tract lengths. Second, existing methods generally require genotypes, which is not feasible to obtain for many next-generation sequencing projects. Third, many methods assume samples are diploid, however a wide variety of sequencing applications will fail to meet this assumption. To address these issues, we introduce a novel hidden Markov model for estimating local ancestry that models the read pileup data, rather than genotypes, is generalized to arbitrary ploidy, and can estimate the time since admixture during local ancestry inference. We demonstrate that our method can simultaneously estimate the time since admixture and local ancestry with good accuracy, and that it performs well on samples of high ploidy—i.e. 100 or more chromosomes. As this method is very general, we expect it will be useful for local ancestry inference in a wider variety of populations than what previously has been possible. We then applied our method to pooled sequencing data derived from populations of Drosophila melanogaster on an ancestry cline on the east coast of North America. We find that regions of local recombination rates are negatively correlated with the proportion of African ancestry, suggesting that selection against foreign ancestry is the least efficient in low recombination regions. Finally we show that clinal outlier loci are enriched for genes associated with gene regulatory functions, consistent with a role of regulatory evolution in ecological adaptation of admixed D. melanogaster populations. Our results illustrate the potential of local ancestry

  3. Differences in early cognitive and receptive-expressive neurodevelopment by ancestry and underlying pathways in Brazil and Argentina.

    PubMed

    Wehby, George L; Trujillo, Antonio J

    2017-02-01

    We examine disparities in early child cognitive and receptive-expressive skills by ethnic ancestry among infants aged 3-24 months from Brazil and Argentina. We employ unique data on the neurodevelopment of children who were seeking routine well-child care at a set of pediatric clinics in these countries. The sample included children who had normal birth outcomes and no major health complications, allowing us to focus on variation in neurodevelopment among children without major physical health limitations. The physicians attending the pediatric clinics were trained in administering the Bayley Infant Neurodevelopmental Screener, a standardized instrument used to screen an infant's risk of neurodevelopmental problems on various domains of abilities. We evaluate disparities in overall neurodevelopmental scores and risk for neurodevelopmental problems as well as in cognitive functioning and receptive-expressive neurodevelopment. We also examine the extent to which household demographic and socioeconomic characteristics and geographic location explain these disparities. We find large gaps in both cognitive and receptive-expressive neurodevelopment by ancestry. In Brazil, children of African ancestry have lower scores on both cognitive and receptive-expressive domains and on overall neurodevelopment than children of European ancestry. In Argentina, children of Native ancestry have lower scores on these outcomes than children of European ancestry. These gaps however are largely explained by differences in geographic location and household characteristics, highlighting the importance of policies that reduce socioeconomic and geographic disparities in social capital and economic development for eliminating ethnic disparities in infant neurodevelopment.

  4. Effects of Type 2 Diabetes on Brain Structure and Cognitive Function: African American–Diabetes Heart Study MIND

    PubMed Central

    Whitlow, C.T.; Sink, K.M.; Divers, J.; Smith, S.C.; Xu, J.; Palmer, N.D.; Hugenschmidt, C.E.; Williamson, J.D.; Bowden, D.W.; Freedman, B.I.; Maldjian, J.A.

    2016-01-01

    BACKGROUND AND PURPOSE Rates of type 2 diabetes are higher among African Americans compared with individuals of European ancestry. The purpose of this investigation was to determine the relationship between MR imaging measures of brain structure (volume of GM, WM, WM lesions) and cognitive function in a population of African Americans with type 2 diabetes. These MR imaging measures of brain structure are affected by type 2 diabetes–associated macrovascular and microvascular disease and may be associated with performance on tasks of cognitive function in the understudied African American population. MATERIALS AND METHODS African Americans with type 2 diabetes enrolled in the African American–Diabetes Heart Study MIND study (n = 263) were evaluated across a broad range of cognitive domains and imaged with brain MR imaging. Associations between cognitive parameters and MR imaging measures of whole-brain GM, WM, and WM lesion volumes were assessed by using adjusted multivariate models. RESULTS Lower GM volume was associated with poorer performance on measures of general cognitive function, working memory, and executive function. Higher WM lesion volume was associated with poorer performance on a smaller subset of cognitive domains compared with GM volume but included aspects of working memory and executive function. There were no statistically significant associations with WM volume. CONCLUSIONS Markers of cortical atrophy and WM lesion volume are associated with cognitive function in African Americans with type 2 diabetes. These associations are described in an African American cohort with disease control similar to that of individuals of European ancestry, rather than underserved African Americans with poor access to health care. Interventions to reduce cortical atrophy and WM disease may improve cognitive outcomes in this understudied population. PMID:26206811

  5. 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

  6. The geography of recent genetic ancestry across Europe.

    PubMed

    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.

  7. Sociodemographic, sociocultural, and individual predictors of reported feelings of meaninglessness among South African adolescents.

    PubMed

    Morojele, Neo K; Brook, Judith S

    2004-12-01

    The purpose of the study was to predict adolescents' sense of meaninglessness about South Africa's sociopolitical situation from sociodemographic, individual level, and sociocultural factors. The participants comprised 39 male and 64 female students from three schools in Cape Town, and had a mean age of 15.2 yr. (SD= 1.8 yr.). They completed an adaptation of Neal and Groat's Meaninglessness scale and measures of sociodemographic (age, sex, and parental occupation, household amenities, and household hunger as proxy measures of socioeconomic status), sociocultural (cultural pride and an adaptation of McClosky and Schaar's anomy scale), and individual level (depression, general life satisfaction, and knowledge of HIV status) factors. A multiple regression analysis indicated that the adolescents with higher reported scores for meaninglessness about South Africa's sociopolitical situation reported lower socioeconomic status, a stronger sense of anomy, and more symptoms of depression.

  8. Coping Strategies as Moderators of the Relation between Individual Race-Related Stress and Mental Health Symptoms for African American Women

    ERIC Educational Resources Information Center

    Greer, Tawanda M.

    2011-01-01

    The purpose of this investigation was to examine coping strategies as moderators of the relationship between individual race-related stress and mental health symptoms among a sample of 128 African American women. Coping strategies refer to efforts used to resolve problems and those used to manage, endure, or alleviate distress. Culture-specific…

  9. Life Experiences of People Who Stutter, and the Perceived Impact of Stuttering on Quality of Life: Personal Accounts of South African Individuals

    ERIC Educational Resources Information Center

    Klompas, Michelle; Ross, Eleanor

    2004-01-01

    The purpose of the study was to investigate the life experiences of a group of South African adults who stutter and the impact of stuttering on their quality of life. Participants were 16 adults with a mean age of 28.9 and ranging from 20 to 59 years. Methods involved individual interviews designed to explore the life domains of education; social…

  10. Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America.

    PubMed

    Kosoy, Roman; Nassir, Rami; Tian, Chao; White, Phoebe A; Butler, Lesley M; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E; Gregersen, Peter K; Belmont, John W; De La Vega, Francisco M; Seldin, Michael F

    2009-01-01

    To provide a resource for assessing continental ancestry in a wide variety of genetic studies, we identified, validated, and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations.

  11. Influence of Genetic Ancestry on INDEL Markers of NFKβ1, CASP8, PAR1, IL4 and CYP19A1 Genes in Leprosy Patients

    PubMed Central

    Pinto, Pablo; Salgado, Claudio; Santos, Ney Pereira Carneiro; Santos, Sidney; Ribeiro-dos-Santos, Ândrea

    2015-01-01

    Background Leprosy is an insidious infectious disease caused by the obligate intracellular bacteria Mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry. Methodology/Principal Findings We investigated the possible effects of CYP19A1 [rs11575899], NFKβ1 [rs28362491], IL1α [rs3783553], CASP8 [rs3834129], UGT1A1 [rs8175347], PAR1 [rs11267092], CYP2E1 [INDEL 96pb] and IL4 [rs79071878] genes in a group of 141 leprosy patients and 180 healthy individuals. The INDELs were typed by PCR Multiplex in ABI PRISM 3130 and analyzed with GeneMapper ID v3.2. The NFKβ1, CASP8, PAR1 and IL4 INDELs were associated with leprosy susceptibility, while NFKβ1, CASP8, PAR1 and CYP19A1 were associated with the MB (Multibacilary) clinical form of leprosy. Conclusions/Significance NFKβ1 [rs28362491], CASP8 [rs3834129], PAR1 [rs11267092] and IL4 [rs79071878] genes are potential markers for susceptibility to leprosy development, while the INDELs in NFKβ1, CASP8, PAR1 and CYP19A1 (rs11575899) are potential markers for the severe clinical form MB. Moreover, all of these markers are influenced by genetic ancestry, and European contribution increases the risk to leprosy development, in other hand an increase in African contribution generates protection against leprosy. PMID:26367014

  12. Perceived Barriers for Accessing Health Services among Individuals with Disability in Four African Countries

    PubMed Central

    Eide, Arne H.; Mannan, Hasheem; Khogali, Mustafa; van Rooy, Gert; Swartz, Leslie; Munthali, Alister; Hem, Karl-Gerhard; MacLachlan, Malcolm; Dyrstad, Karin

    2015-01-01

    There is an increasing awareness among researchers and others that marginalized and vulnerable groups face problems in accessing health care. Access problems in particular in low-income countries may jeopardize the targets set by the United Nations through the Millennium Development Goals. Thus, identifying barriers for individuals with disability in accessing health services is a research priority. The current study aimed at identifying the magnitude of specific barriers, and to estimate the impact of disability on barriers for accessing health care in general. A population based household survey was carried out in Sudan, Namibia, Malawi, and South Africa, including a total of 9307 individuals. The sampling strategy was a two-stage cluster sampling within selected geographical areas in each country. A listing procedure to identify households with disabled members using the Washington Group six screening question was followed by administering household questionnaires in households with and without disabled members, and questionnaires for individuals with and without disability. The study shows that lack of transport, availability of services, inadequate drugs or equipment, and costs, are the four major barriers for access. The study also showed substantial variation in perceived barriers, reflecting largely socio-economic differences between the participating countries. Urbanity, socio-economic status, and severity of activity limitations are important predictors for barriers, while there is no gender difference. It is suggested that education reduces barriers to health services only to the extent that it reduces poverty. Persons with disability face additional and particular barriers to health services. Addressing these barriers requires an approach to health that stresses equity over equality. PMID:25993307

  13. Small individual loans and mental health: a randomized controlled trial among South African adults

    PubMed Central

    Fernald, Lia CH; Hamad, Rita; Karlan, Dean; Ozer, Emily J; Zinman, Jonathan

    2008-01-01

    Background In the developing world, access to small, individual loans has been variously hailed as a poverty-alleviation tool – in the context of "microcredit" – but has also been criticized as "usury" and harmful to vulnerable borrowers. Prior studies have assessed effects of access to credit on traditional economic outcomes for poor borrowers, but effects on mental health have been largely ignored. Methods Applicants who had previously been rejected (n = 257) for a loan (200% annual percentage rate – APR) from a lender in South Africa were randomly assigned to a "second-look" that encouraged loan officers to approve their applications. This randomized encouragement resulted in 53% of applicants receiving a loan they otherwise would not have received. All subjects were assessed 6–12 months later with questions about demographics, socio-economic status, and two indicators of mental health: the Center for Epidemiologic Studies – Depression Scale (CES-D) and Cohen's Perceived Stress scale. Intent-to-treat analyses were calculated using multinomial probit regressions. Results Randomization into receiving a "second look" for access to credit increased perceived stress in the combined sample of women and men; the findings were stronger among men. Credit access was associated with reduced depressive symptoms in men, but not women. Conclusion Our findings suggest that a mechanism used to reduce the economic stress of extremely poor individuals can have mixed effects on their experiences of psychological stress and depressive symptomatology. Our data support the notion that mental health should be included as a measure of success (or failure) when examining potential tools for poverty alleviation. Further longitudinal research is needed in South Africa and other settings to understand how borrowing at high interest rates affects gender roles and daily life activities. CCT: ISRCTN 10734925 PMID:19087316

  14. Application of FORDISC 3.0 to explore differences among crania of North American and South African blacks and whites.

    PubMed

    L'Abbé, Ericka N; Kenyhercz, Michael; Stull, Kyra E; Keough, Natalie; Nawrocki, Stephen

    2013-11-01

    Using discriminant function analysis, classification accuracies for ancestry and sex in white and black South Africans were compared using North American (FDB), African groups in Howells (HDB), and South African (SADB) databases in FORDISC 3.0. (FD3). Twenty-four standard linear measures were collected from a total of 86 black and 101 white crania obtained from the Pretoria Bone Collection. White and black South Africans classified 73% correctly in FDB, 55% correctly in HDB, and 71% correctly in SADB. The percentage of atypical cases was higher with FDB than SADB. In all three databases, misclassification occurred more with sex than ancestry revealing differences in sexual dimorphism between population groups. Broad ancestral differences may explain low misclassification rates for ancestry. FD3, with a modern South African reference sample, can assist South African anthropologists to standardize methodology and to justify procedures for estimating ancestry.

  15. Rare, low frequency, and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans

    PubMed Central

    Olfson, Emily; Saccone, Nancy L.; Johnson, Eric O.; Chen, Li-Shiun; Culverhouse, Robert; Doheny, Kimberly; Foltz, Steven M.; Fox, Louis; Gogarten, Stephanie M.; Hartz, Sarah; Hetrick, Kurt; Laurie, Cathy C.; Marosy, Beth; Amin, Najaf; Arnett, Donna; Barr, R. Graham; Bartz, Traci M.; Bertelsen, Sarah; Borecki, Ingrid B.; Brown, Michael R.; Chasman, Daniel I.; van Duijn, Cornelia M.; Feitosa, Mary F.; Fox, Ervin R.; Franceschini, Nora; Franco, Oscar H.; Grove, Megan L.; Guo, Xiuqing; Hofman, Albert; Kardia, Sharon L.R.; Morrison, Alanna C.; Musani, Solomon K.; Psaty, Bruce M.; Rao, D.C.; Reiner, Alex P.; Rice, Kenneth; Ridker, Paul M.; Rose, Lynda M.; Schick, Ursula M.; Schwander, Karen; Uitterlinden, Andre G.; Vojinovic, Dina; Wang, Jen-Chyong; Ware, Erin B.; Wilson, Gregory; Yao, Jie; Zhao, Wei; Breslau, Naomi; Hatsukami, Dorothy; Stitzel, Jerry A.; Rice, John; Goate, Alison; Bierut, Laura J.

    2015-01-01

    The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine dependent cases (Fagerström Test for Nicotine Dependence score≥4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (MAF≥0.05), aggregate low frequency variants (0.05>MAF≥0.005), and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180X coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: OR=1.3, p=3.5×10−11; African ancestry: OR=1.3, p=0.01) and demonstrated that 3 low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, p=0.005; African ancestry: OR=1.4, p=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, p=0.01) and in the same risk direction in African Americans (OR=1.5, p=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence risk for smoking-related diseases such as lung cancer. PMID:26239294

  16. Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

    PubMed

    Olfson, E; Saccone, N L; Johnson, E O; Chen, L-S; Culverhouse, R; Doheny, K; Foltz, S M; Fox, L; Gogarten, S M; Hartz, S; Hetrick, K; Laurie, C C; Marosy, B; Amin, N; Arnett, D; Barr, R G; Bartz, T M; Bertelsen, S; Borecki, I B; Brown, M R; Chasman, D I; van Duijn, C M; Feitosa, M F; Fox, E R; Franceschini, N; Franco, O H; Grove, M L; Guo, X; Hofman, A; Kardia, S L R; Morrison, A C; Musani, S K; Psaty, B M; Rao, D C; Reiner, A P; Rice, K; Ridker, P M; Rose, L M; Schick, U M; Schwander, K; Uitterlinden, A G; Vojinovic, D; Wang, J-C; Ware, E B; Wilson, G; Yao, J; Zhao, W; Breslau, N; Hatsukami, D; Stitzel, J A; Rice, J; Goate, A; Bierut, L J

    2016-05-01

    The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.

  17. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

    PubMed Central

    Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

    2017-01-01

    Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

  18. Chromosome Connections: Compelling Clues to Common Ancestry

    ERIC Educational Resources Information Center

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  19. Proving universal common ancestry with similar sequences

    PubMed Central

    Martins, Leonardo de Oliveira; Posada, David

    2013-01-01

    Douglas Theobald recently developed an interesting test putatively capable of quantifying the evidence for a Universal Common Ancestry uniting the three domains of life (Eukarya, Archaea and Bacteria) against hypotheses of Independent Origins for some of these domains. We review here his model, in particular in relation to the treatment of Horizontal Gene Transfer (HGT) and to the quality of sequence alignment. PMID:23814665

  20. Unravelling the distinct strains of Tharu ancestry

    PubMed Central

    Chaubey, Gyaneshwer; Singh, Manvendra; Crivellaro, Federica; Tamang, Rakesh; Nandan, Amrita; Singh, Kamayani; Sharma, Varun Kumar; Pathak, Ajai Kumar; Shah, Anish M; Sharma, Vishwas; Singh, Vipin Kumar; Selvi Rani, Deepa; Rai, Niraj; Kushniarevich, Alena; Ilumäe, Anne-Mai; Karmin, Monika; Phillip, Anand; Verma, Abhilasha; Prank, Erik; Singh, Vijay Kumar; Li, Blaise; Govindaraj, Periyasamy; Chaubey, Akhilesh Kumar; Dubey, Pavan Kumar; Reddy, Alla G; Premkumar, Kumpati; Vishnupriya, Satti; Pande, Veena; Parik, Jüri; Rootsi, Siiri; Endicott, Phillip; Metspalu, Mait; Lahr, Marta Mirazon; van Driem, George; Villems, Richard; Kivisild, Toomas; Singh, Lalji; Thangaraj, Kumarasamy

    2014-01-01

    The northern region of the Indian subcontinent is a vast landscape interlaced by diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great number of ethnic groups are found there, displaying a multitude of languages and cultures. The Tharu is one of the largest and most linguistically diverse of such groups, scattered across the Tarai region of Nepal and bordering Indian states. Their origins are uncertain. Hypotheses have been advanced postulating shared ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan languages, but have traditionally been described by ethnographers as representing East Asian phenotype. Their ancestry and intra-population diversity has previously been tested only for haploid (mitochondrial DNA and Y-chromosome) markers in a small portion of the population. This study presents the first systematic genetic survey of the Tharu from both Nepal and two Indian states of Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We show that the Tharu have dual genetic ancestry as up to one-half of their gene pool is of East Asian origin. Within the South Asian proportion of the Tharu genetic ancestry, we see vestiges of their common origin in the north of the South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43. PMID:24667789

  1. Social distance and stigma toward individuals with schizophrenia: findings in an urban, African-American community sample.

    PubMed

    Broussard, Beth; Goulding, Sandra M; Talley, Colin L; Compton, Michael T

    2012-11-01

    Because schizophrenia is arguably among the most stigmatized health conditions, research assessing correlates of stigma is essential. This study examined factors associated with stigma in predominantly Protestant, low-income, urban African Americans in the Southeastern United States. A survey was distributed to 282 patrons of an inner-city food court/farmers' market. Associations were assessed between two measures of stigma--an adapted version of the Social Distance Scale (SDS) and a Semantic Differential Measure (SDM) of attributes such as dangerousness, dirtiness, and worthlessness--and several key variables addressing sociodemographic characteristics and exposure to/familiarity with mental illnesses. Independent predictors of scores on the two measures were identified using linear regression modeling. Higher stigma (as measured by the SDM) was predicted by a family history of psychiatric treatment, whereas lower stigma (as indicated by the SDS) was predicted by personal psychiatric treatment history and higher annual income. The results suggest special considerations when working with disenfranchised populations, especially family members of individuals with mental illnesses, in treatment settings.

  2. The metabolic effects of a commercially available chicken peri-peri (African bird's eye chilli) meal in overweight individuals.

    PubMed

    Kroff, Jacolene; Hume, David J; Pienaar, Paula; Tucker, Ross; Lambert, Estelle V; Rae, Dale E

    2017-03-01

    A growing body of evidence suggests that capsaicin ingestion may lead to desirable metabolic outcomes; however, the results in humans are equivocal. Whether or not benefits may be gained from ingestion of capsaicin via a commercially available meal has not been determined. The objectives of this randomised, cross-over intervention study were to compare the 2 h postprandial effects of a standard commercially prepared meal containing chilli (HOT, 5·82 mg total capsaicinoids) with a similar meal with no chilli (CON, 25 kg/m2 and a waist circumference >94 cm (men) or 80 cm (women), were studied. Participants had normal glucose tolerance and were accustomed, but were not regular chilli eaters. A paired t test indicated that insulin AUC was smaller following the HOT meal (P=0·002). Similarly, there was a tendency for glucose AUC to be reduced following the HOT meal (P=0·056). No discernable effects of the HOT meal were observed on metabolic rate, core temperature, hs-CRP concentrations and endothelial-dependent microvascular reactivity. The results from this study indicate that a standard restaurant meal containing a relatively small dose of capsaicin delivered via African bird's eye chilli, which is currently available to the public, results in lower postprandial insulin concentrations in overweight individuals, compared with the same meal without chilli.

  3. Recruiting African American Churches to Participate in Research: The Learning and Developing Individual Exercise Skills for a Better Life Study

    PubMed Central

    Whitt-Glover, Melicia C.; Borden, Shanice L.; Alexander, Dayna S.; Kennedy, Betty M.; Goldmon, Moses V.

    2016-01-01

    Physical activity among African Americans (AA) is low; effective intervention strategies are needed. Community-based settings are useful for delivering health-related interventions in racial/ethnic minority communities. This article describes strategies used to recruit churches for participation in a 22-month intervention designed to increase physical activity levels in AA women. Initial recruitment efforts, led by AA study staff, included direct mailers, phone calls, and in-person meetings with church representatives. After 10 months, only five churches were enrolled. Seven community members with existing partnerships/contacts in the faith community were subsequently hired and an additional 26 churches were enrolled within 6 months. Overall response rate was 45%, and churches required 3.5 ± 3.0 months of multiple contacts prior to enrollment. The main primary contacts within churches were individuals with personal interest in the program and pastors. Prior relationship between the research team and churches did not appear to influence church enrollment as much as community member recruiters. The current study identifies several potential strategies that may be useful for increasing success in efforts to recruit AA churches into studies. Additional research is warranted that tests and compares a variety of recruitment strategies to determine the most successful strategies for recruitment in different populations. PMID:26724311

  4. Forensic Applicability of Femur Subtrochanteric Shape to Ancestry Assessment in Thai and White American Males.

    PubMed

    Tallman, Sean D; Winburn, Allysha P

    2015-09-01

    Ancestry assessment from the postcranial skeleton presents a significant challenge to forensic anthropologists. However, metric dimensions of the femur subtrochanteric region are believed to distinguish between individuals of Asian and non-Asian descent. This study tests the discriminatory power of subtrochanteric shape using modern samples of 128 Thai and 77 White American males. Results indicate that the samples' platymeric index distributions are significantly different (p≤0.001), with the Thai platymeric index range generally lower and the White American range generally higher. While the application of ancestry assessment methods developed from Native American subtrochanteric data results in low correct classification rates for the Thai sample (50.8-57.8%), adapting these methods to the current samples leads to better classification. The Thai data may be more useful in forensic analysis than previously published subtrochanteric data derived from Native American samples. Adapting methods to include appropriate geographic and contemporaneous populations increases the accuracy of femur subtrochanteric ancestry methods.

  5. Cattle ancestry in bison: explanations for higher mtDNA than autosomal ancestry.

    PubMed

    Hedrick, Philip W

    2010-08-01

    Understanding and documenting the process of hybridization and introgression between related species is a major focus of recent evolutionary research using molecular techniques. Many North American bison herds have cattle ancestry introduced by crossbreeding over a century ago. Molecular estimates of this ancestry have shown much higher levels for cattle mtDNA than for autosomal cattle genes. A large part of this difference appears to be the result of partial reproductive isolation between the two species where only bison bull x domestic cow crosses are successful, and all the surviving progeny are females. In addition, selection against autosomal cattle genes in bison may have contributed to differential levels of cattle ancestry. The impact of selection against cattle mtDNA and gene flow of bison mtDNA are examined to explain particular combinations of mtDNA and autosomal cattle ancestry. A bottleneck, after the level of cattle ancestry in bison was reduced to a low level, is consistent with the high variance over autosomal loci observed for cattle ancestry, and differential selection among cattle loci in bison does not need to be invoked. Further examination of the cattle genome in bison may shed light on whether these markers, or their associated regions, are indeed neutral.

  6. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes

    PubMed Central

    Florez, J. C.; Price, A. L.; Campbell, D.; Riba, L.; Parra, M. V.; Yu, F.; Duque, C.; Saxena, R.; Gallego, N.; Tello-Ruiz, M.; Franco, L.; Rodríguez-Torres, M.; Villegas, A.; Bedoya, G.; Aguilar-Salinas, C. A.; Tusié-Luna, M. T.; Ruiz-Linares, A.; Reich, D.

    2011-01-01

    Aims/hypothesis Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. Methods We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Results Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02–0.21], p=2.0 × 10−5) and Colombians (OR 0.26 [0.08–0.78], p=0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19–2.12], p=0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04–0.71], p=0.02). Adjustment for BMI did not change the results. Conclusions/interpretation The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects. PMID:19526211

  7. Disease, predation and demography: Assessing the impacts of bovine tuberculosis on African buffalo by monitoring at individual and population levels

    USGS Publications Warehouse

    Cross, P.C.; Heisey, D.M.; Bowers, J.A.; Hay, C.T.; Wolhuter, J.; Buss, P.; Hofmeyr, M.; Michel, A.L.; Bengis, Roy G.; Bird, T.L.F.; Du Toit, J.T.; Getz, W.M.

    2009-01-01

    1. Understanding the effects of disease is critical to determining appropriate management responses, but estimating those effects in wildlife species is challenging. We used bovine tuberculosis (BTB) in the African buffalo Syncerus caffer population of Kruger National Park, South Africa, as a case study to highlight the issues associated with estimating chronic disease effects in a long-lived host. 2. We used known and radiocollared buffalo, aerial census data, and a natural gradient in pathogen prevalence to investigate if: (i) at the individual level, BTB infection reduces reproduction; (ii) BTB infection increases vulnerability to predation; and (iii) at the population level, increased BTB prevalence causes reduced population growth. 3. There was only a marginal reduction in calving success associated with BTB infection, as indexed by the probability of sighting a known adult female with or without a calf (P = 0??065). 4. Since 1991, BTB prevalence increased from 27 to 45% in the southern region and from 4 to 28% in the central region of Kruger National Park. The prevalence in the northern regions was only 1??5% in 1998. Buffalo population growth rates, however, were neither statistically different among regions nor declining over time. 5. Lions Panthera leo did not appear to preferentially kill test-positive buffalo. The best (Akaike's Information Criterion corrected for small sample size) AICc model with BTB as a covariate [exp(??) = 0??49; 95% CI = (0??24-1??02)] suggested that the mortality hazard for positive individuals was no greater than for test-negative individuals. 6. Synthesis and applications. Test accuracy, time-varying disease status, and movement among populations are some of the issues that make the detection of chronic disease impacts challenging. For these reasons, the demographic impacts of bovine tuberculosis in the Kruger National Park remain undetectable despite 6 years of study on known individuals and 40 years of population counts

  8. Exploring the Y Chromosomal Ancestry of Modern Panamanians

    PubMed Central

    Grugni, Viola; Battaglia, Vincenza; Perego, Ugo Alessandro; Raveane, Alessandro; Lancioni, Hovirag; Olivieri, Anna; Ferretti, Luca; Woodward, Scott R.; Pascale, Juan Miguel; Cooke, Richard; Myres, Natalie; Motta, Jorge; Torroni, Antonio; Achilli, Alessandro; Semino, Ornella

    2015-01-01

    Geologically, Panama belongs to the Central American land-bridge between North and South America crossed by Homo sapiens >14 ka ago. Archaeologically, it belongs to a wider Isthmo-Colombian Area. Today, seven indigenous ethnic groups account for 12.3% of Panama’s population. Five speak Chibchan languages and are characterized by low genetic diversity and a high level of differentiation. In addition, no evidence of differential structuring between maternally and paternally inherited genes has been reported in isthmian Chibchan cultural groups. Recent data have shown that 83% of the Panamanian general population harbour mitochondrial DNAs (mtDNAs) of Native American ancestry. Considering differential male/female mortality at European contact and multiple degrees of geographical and genetic isolation over the subsequent five centuries, the Y-chromosome Native American component is expected to vary across different geographic regions and communities in Panama. To address this issue, we investigated Y-chromosome variation in 408 modern males from the nine provinces of Panama and one indigenous territory (the comarca of Kuna Yala). In contrast to mtDNA data, the Y-chromosome Native American component (haplogroup Q) exceeds 50% only in three populations facing the Caribbean Sea: the comarca of Kuna Yala and Bocas del Toro province where Chibchan languages are spoken by the majority, and the province of Colón where many Kuna and people of mixed indigenous-African-and-European descent live. Elsewhere the Old World component is dominant and mostly represented by western Eurasian haplogroups, which signal the strong male genetic impact of invaders. Sub-Saharan African input accounts for 5.9% of male haplotypes. This reflects the consequences of the colonial Atlantic slave trade and more recent influxes of West Indians of African heritage. Overall, our findings reveal a local evolution of the male Native American ancestral gene pool, and a strong but geographically

  9. Differences in Albuminuria between Hispanics and Whites: An Evaluation by Genetic Ancestry and Country of Origin: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Peralta, Carmen A.; Li, Yongmei; Wassel, Christina; Choudhry, Shweta; Palmas, Walter; Seldin, Michael F.; Risch, Neil; Siscovick, David; Arnett, Donna; Psaty, Bruce; Shlipak, Michael G.

    2010-01-01

    Background Reports show higher prevalence of albuminuria among Hispanics compared to whites. Differences by country of origin or genetic background are unknown. Methods and Results In MESA, we studied the associations of both genetic ancestry and country of origin with albumin to creatinine ratio among 1,417 Hispanic vs. White participants using multivariable linear regression and back transforming beta-coefficients into relative difference (%RD, 95%CI). Percentage European, Native American and African ancestry components for Hispanics were estimated using genetic admixture analysis. The proportions of European, Native American and African genetic ancestry differed significantly by country of origin (p-value<0.0001); Mexican/Central Americans had the highest Native American (41±13%), Puerto Ricans had the highest European (61±15 %), and Dominicans had the highest African (39±21%) ancestry. Hispanic ethnicity was associated with higher albumin/creatinine ratio compared to whites, but the association varied country of origin (adjusted p interaction=0.04). Mexican/Central Americans and Dominicans had higher albumin/creatinine ratio compared to whites after adjustment (RD 19%, 2-40% and (RD 27%, 1-61%), but not Puerto Ricans (RD 8%, −12-34%). Higher Native American ancestry was associated with higher albuminuria after age and sex adjustment among all Hispanics (RD 11%, 1-21%), but was attenuated after further adjustment. Higher European ancestry was independently associated with lower albumin/creatinine ratio among Puerto Ricans (−21%, −34 to −6), but not among Mexican/Central Americans and Dominicans. Conclusions Hispanics are a heterogeneous group with varying genetic ancestry. Risks of albuminuria differ across country of origin groups. These differences may be due, in part, to differences in genetic ancestral components. PMID:20445135

  10. The Great Migration and African-American Genomic Diversity.

    PubMed

    Baharian, Soheil; Barakatt, Maxime; Gignoux, Christopher R; Shringarpure, Suyash; Errington, Jacob; Blot, William J; Bustamante, Carlos D; Kenny, Eimear E; Williams, Scott M; Aldrich, Melinda C; Gravel, Simon

    2016-05-01

    We present a comprehensive assessment of genomic diversity in the African-American population by studying three genotyped cohorts comprising 3,726 African-Americans from across the United States that provide a representative description of the population across all US states and socioeconomic status. An estimated 82.1% of ancestors to African-Americans lived in Africa prior to the advent of transatlantic travel, 16.7% in Europe, and 1.2% in the Americas, with increased African ancestry in the southern United States compared to the North and West. Combining demographic models of ancestry and those of relatedness suggests that admixture occurred predominantly in the South prior to the Civil War and that ancestry-biased migration is responsible for regional differences in ancestry. We find that recent migrations also caused a strong increase in genetic relatedness among geographically distant African-Americans. Long-range relatedness among African-Americans and between African-Americans and European-Americans thus track north- and west-bound migration routes followed during the Great Migration of the twentieth century. By contrast, short-range relatedness patterns suggest comparable mobility of ∼15-16km per generation for African-Americans and European-Americans, as estimated using a novel analytical model of isolation-by-distance.

  11. The Great Migration and African-American Genomic Diversity

    PubMed Central

    Barakatt, Maxime; Gignoux, Christopher R.; Errington, Jacob; Blot, William J.; Bustamante, Carlos D.; Kenny, Eimear E.; Williams, Scott M.; Aldrich, Melinda C.; Gravel, Simon

    2016-01-01

    We present a comprehensive assessment of genomic diversity in the African-American population by studying three genotyped cohorts comprising 3,726 African-Americans from across the United States that provide a representative description of the population across all US states and socioeconomic status. An estimated 82.1% of ancestors to African-Americans lived in Africa prior to the advent of transatlantic travel, 16.7% in Europe, and 1.2% in the Americas, with increased African ancestry in the southern United States compared to the North and West. Combining demographic models of ancestry and those of relatedness suggests that admixture occurred predominantly in the South prior to the Civil War and that ancestry-biased migration is responsible for regional differences in ancestry. We find that recent migrations also caused a strong increase in genetic relatedness among geographically distant African-Americans. Long-range relatedness among African-Americans and between African-Americans and European-Americans thus track north- and west-bound migration routes followed during the Great Migration of the twentieth century. By contrast, short-range relatedness patterns suggest comparable mobility of ∼15–16km per generation for African-Americans and European-Americans, as estimated using a novel analytical model of isolation-by-distance. PMID:27232753

  12. Genetic architecture of skin and eye color in an African-European admixed population.

    PubMed

    Beleza, Sandra; Johnson, Nicholas A; Candille, Sophie I; Absher, Devin M; Coram, Marc A; Lopes, Jailson; Campos, Joana; Araújo, Isabel Inês; Anderson, Tovi M; Vilhjálmsson, Bjarni J; Nordborg, Magnus; Correia E Silva, António; Shriver, Mark D; Rocha, Jorge; Barsh, Gregory S; Tang, Hua

    2013-03-01

    Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3 × 10(-62), SLC24A5 P = 9.6 × 10(-9)) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4 × 10(-27), TYR P = 1.1 × 10(-9), APBA2[OCA2] P = 1.5 × 10(-8), SLC45A2 P = 6 × 10(-9)) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

  13. The Effects of Socioeconomic Status, Clinical Factors, and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

    PubMed Central

    Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.

    2014-01-01

    Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

  14. The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

    PubMed

    Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

    2014-01-01

    Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

  15. Russia's Literary Genius Alexander Pushkin: The Great-Grandson of an African Slave.

    ERIC Educational Resources Information Center

    Lounsbery, Anne

    2000-01-01

    Alexander Pushkin, Russia's most celebrated literary figure, descended from an African slave. On both parents' sides, he was related to Avram Petrovich Gannibal, who was born to an African prince and abducted to become a slave to a Russian diplomat. Pushkin chose to pride himself on both his aristocratic life and his African ancestry. (SM)

  16. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals.

    PubMed

    Siffert, W; Forster, P; Jöckel, K H; Mvere, D A; Brinkmann, B; Naber, C; Crookes, R; Du P Heyns, A; Epplen, J T; Fridey, J; Freedman, B I; Müller, N; Stolke, D; Sharma, A M; Al Moutaery, K; Grosse-Wilde, H; Buerbaum, B; Ehrlich, T; Ahmad, H R; Horsthemke, B; Du Toit, E D; Tiilikainen, A; Ge, J; Wang, Y; Rosskopf, D

    1999-09-01

    Recently, it was demonstrated that one allele (825T) of the gene encoding the G protein beta3 subunit (GNB3) is associated with hypertension in Germans. This study investigates a possible association with obesity in young male Germans, Chinese, and black South Africans with low, intermediate, and high 825T allele frequencies, respectively. In each of these three distinct cohorts, the 825T allele frequency was increased significantly in overweight (body mass index [BMI] > or =25 kg/m2) and obese individuals (BMI >27 kg/m2) compared to those with normal weight. The 825T allele frequencies in these three BMI groups were, respectively, 29.5, 39.3, and 47.7% in Germans, 46.8, 53.9, and 58.6% in Chinese, and 83.1, 87.7, and 90.9% in South Africans. In each of these three distinct groups, the 825T allele was significantly associated with obesity with odds ratios between 2 and 3. More urban than rural black Africans were overweight despite similar 825T allele frequencies in both populations, which underscores the role of both genetic and environmental factors. BP values in young male whites increased significantly with increasing BMI values but were independent of the C825T polymorphism, suggesting that hypertension associated with the 825T allele could be a consequence of obesity. Genotyping of 5254 individuals from 55 native population samples from Africa, the Americas, Europe, Asia, Australia, and New Guinea demonstrated highest 825T allele frequencies in black Africans (82%) and intermediate values in east Asians (47%). It is anticipated that high frequencies of the 825T allele in Africans and Asians may contribute to an obesity and hypertension epidemic if Westernization of lifestyles continues.

  17. The Mosaic Ancestry of the Drosophila Genetic Reference Panel and the D. melanogaster Reference Genome Reveals a Network of Epistatic Fitness Interactions.

    PubMed

    Pool, John E

    2015-12-01

    North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa-Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations.

  18. Anthropologists' views on race, ancestry, and genetics

    PubMed Central

    Yu, Joon‐Ho; Ifekwunigwe, Jayne O.; Harrell, Tanya M.; Bamshad, Michael J.; Royal, Charmaine D.

    2016-01-01

    Abstract Controversies over race conceptualizations have been ongoing for centuries and have been shaped, in part, by anthropologists. Objective To assess anthropologists' views on race, genetics, and ancestry. Methods In 2012 a broad national survey of anthropologists examined prevailing views on race, ancestry, and genetics. Results Results demonstrate consensus that there are no human biological races and recognition that race exists as lived social experiences that can have important effects on health. Discussion Racial privilege affects anthropologists' views on race, underscoring the importance that anthropologists be vigilant of biases in the profession and practice. Anthropologists must mitigate racial biases in society wherever they might be lurking and quash any sociopolitical attempts to normalize or promote racist rhetoric, sentiment, and behavior. PMID:27874171

  19. AncestrySNPminer: A bioinformatics tool to retrieve and develop ancestry informative SNP panels

    PubMed Central

    Amirisetty, Sushil; Khurana Hershey, Gurjit K.; Baye, Tesfaye M.

    2012-01-01

    A wealth of genomic information is available in public and private databases. However, this information is underutilized for uncovering population specific and functionally relevant markers underlying complex human traits. Given the huge amount of SNP data available from the annotation of human genetic variation, data mining is a faster and cost effective approach for investigating the number of SNPs that are informative for ancestry. In this study, we present AncestrySNPminer, the first web-based bioinformatics tool specifically designed to retrieve Ancestry Informative Markers (AIMs) from genomic data sets and link these informative markers to genes and ontological annotation classes. The tool includes an automated and simple “scripting at the click of a button” functionality that enables researchers to perform various population genomics statistical analyses methods with user friendly querying and filtering of data sets across various populations through a single web interface. AncestrySNPminer can be freely accessed at https://research.cchmc.org/mershalab/AncestrySNPminer/login.php. PMID:22584067

  20. Exploring iris colour prediction and ancestry inference in admixed populations of South America.

    PubMed

    Freire-Aradas, A; Ruiz, Y; Phillips, C; Maroñas, O; Söchtig, J; Tato, A Gómez; Dios, J Álvarez; de Cal, M Casares; Silbiger, V N; Luchessi, A D; Luchessi, A D; Chiurillo, M A; Carracedo, Á; Lareu, M V

    2014-11-01

    New DNA-based predictive tests for physical characteristics and inference of ancestry are highly informative tools that are being increasingly used in forensic genetic analysis. Two eye colour prediction models: a Bayesian classifier - Snipper and a multinomial logistic regression (MLR) system for the Irisplex assay, have been described for the analysis of unadmixed European populations. Since multiple SNPs in combination contribute in varying degrees to eye colour predictability in Europeans, it is likely that these predictive tests will perform in different ways amongst admixed populations that have European co-ancestry, compared to unadmixed Europeans. In this study we examined 99 individuals from two admixed South American populations comparing eye colour versus ancestry in order to reveal a direct correlation of light eye colour phenotypes with European co-ancestry in admixed individuals. Additionally, eye colour prediction following six prediction models, using varying numbers of SNPs and based on Snipper and MLR, were applied to the study populations. Furthermore, patterns of eye colour prediction have been inferred for a set of publicly available admixed and globally distributed populations from the HGDP-CEPH panel and 1000 Genomes databases with a special emphasis on admixed American populations similar to those of the study samples.

  1. Admixture mapping scans identify a locus affecting retinal vascular caliber in hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

    PubMed

    Cheng, Ching-Yu; Reich, David; Wong, Tien Y; Klein, Ronald; Klein, Barbara E K; Patterson, Nick; Tandon, Arti; Li, Man; Boerwinkle, Eric; Sharrett, A Richey; Kao, W H Linda

    2010-04-15

    Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (rho = 0.071, P = 0.003), but not CRAE (rho = 0.032, P = 0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = -0.73) or CRVE (genome-wide score = -0.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 microm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity <0.001). Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension.

  2. Dental morphology and ancestry in Albuquerque, New Mexico Hispanics.

    PubMed

    Willermet, C M; Edgar, H J H

    2009-01-01

    The term "Hispanic" groups people from Central and South America and the Caribbean, combining disparate cultures, languages, and ancestry, and masking biological differences. Historical and current admixture patterns within these populations and with indigenous and European-, African-, and/or Asian- derived populations complicate the biological picture. Although "Hispanic" has little biological meaning, it is used widely in epidemiology, disease management, and forensics as a biologically significant group. An interdisciplinary approach combining historical, cultural, and biological data can characterize regional and temporal differences between Hispanic populations. We examined biological distances with a population of central New Mexico Hispanics, as a case study of the local specificity of population history. We collected dental morphological trait frequencies from samples of recent Albuquerque-area Hispanic Americans and several ancestral and contemporary groups. To explore regional admixture patterns we calculated biological distances using the modified Mahalanobis D(2) statistic. Our results indicate that Albuquerque Hispanics are more similar to their European and African ancestral groups than to Native Americans in New Mexico. Additionally, their affinity to Native Americans is greater with prehistoric rather than contemporary samples. We argue that these results reflect a local rather than pan-Hispanic admixture pattern; they underscore that populations are better understood at the local and regional levels. It is undesirable to make sweeping biological generalizations for groups known to be geographically and genetically disparate. This research is part of a growing trend in biological research concerning Hispanics and other groups-an emphasis on local samples, informed by historical, cultural, and biological factors.

  3. African-American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups

    PubMed Central

    Ely, Bert; Wilson, Jamie Lee; Jackson, Fatimah; Jackson, Bruce A

    2006-01-01

    Background Mitochondrial DNA (mtDNA) haplotypes have become popular tools for tracing maternal ancestry, and several companies offer this service to the general public. Numerous studies have demonstrated that human mtDNA haplotypes can be used with confidence to identify the continent where the haplotype originated. Ideally, mtDNA haplotypes could also be used to identify a particular country or ethnic group from which the maternal ancestor emanated. However, the geographic distribution of mtDNA haplotypes is greatly influenced by the movement of both individuals and population groups. Consequently, common mtDNA haplotypes are shared among multiple ethnic groups. We have studied the distribution of mtDNA haplotypes among West African ethnic groups to determine how often mtDNA haplotypes can be used to reconnect Americans of African descent to a country or ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA hypervariable segment I (HVS-I) usually provides sufficient information to assign a particular mtDNA to the proper haplogroup, and it contains most of the variation that is available to distinguish a particular mtDNA haplotype from closely related haplotypes. In this study, samples of general African-American and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches recorded for each sample. Results When two independent African-American samples were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly matched common haplotypes that were shared among multiple African ethnic groups. Another 40% did not match any sequence in the database, and fewer than 10% were an exact match to a sequence from a single African ethnic group. Differences in the regional distribution of haplotypes were observed in the African database, and the African-American haplotypes were more likely to match haplotypes found in ethnic groups from

  4. Age at onset of multiple sclerosis may be influenced by place of residence during childhood rather than ancestry.

    PubMed

    Kennedy, J; O'Connor, P; Sadovnick, A D; Perara, M; Yee, I; Banwell, B

    2006-01-01

    Multiple sclerosis (MS) most commonly affects individuals of Northern European descent who live in countries at high latitude. The relative contributions of ancestry, country of birth and residence as determinants of MS risk have been studied in adult MS, but have not been explored in the pediatric MS population. In this study, we compare the demographics of pediatric- and adult-onset MS patients cared for in Toronto, Ontario, Canada, a multicultural region. The country of birth, residence during childhood, and ancestry were compared for 44 children and 573 adults. Our results demonstrate that although both the pediatric and adult cohorts were essentially born and raised in the same region of Ontario, Canada, children with MS were more likely to report Caribbean, Asian or Middle Eastern ancestry, and were less likely to have European heritage compared with individuals with adult-onset MS. The difference in ancestry between the pediatric and adult MS cohorts can be explained by two hypotheses: (1) individuals raised in a region of high MS prevalence, but whose ancestors originate from regions in which MS is rare, have an earlier age of MS onset, and (2) the place of residence during childhood, irrespective of ancestry, determines lifetime MS risk -- a fact that will be reflected in a change in the demographics of the adult MS cohort in our region as Canadian-raised children of recent immigrants reach the typical age of adult-onset MS.

  5. Using ancestry matching to combine family-based and unrelated samples for genome-wide association studies.

    PubMed

    Crossett, Andrew; Kent, Brian P; Klei, Lambertus; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn; Devlin, Bernie

    2010-12-10

    We propose a method to analyze family-based samples together with unrelated cases and controls. The method builds on the idea of matched case-control analysis using conditional logistic regression (CLR). For each trio within the family, a case (the proband) and matched pseudo-controls are constructed, based upon the transmitted and untransmitted alleles. Unrelated controls, matched by genetic ancestry, supplement the sample of pseudo-controls; likewise unrelated cases are also paired with genetically matched controls. Within each matched stratum, the case genotype is contrasted with control/pseudo-control genotypes via CLR, using a method we call matched-CLR (mCLR). Eigenanalysis of numerous SNP genotypes provides a tool for mapping genetic ancestry. The result of such an analysis can be thought of as a multidimensional map, or eigenmap, in which the relative genetic similarities and differences amongst individuals is encoded in the map. Once constructed, new individuals can be projected onto the ancestry map based on their genotypes. Successful differentiation of individuals of distinct ancestry depends on having a diverse, yet representative sample from which to construct the ancestry map. Once samples are well-matched, mCLR yields comparable power to competing methods while ensuring excellent control over Type I error.

  6. Using ancestry matching to combine family-based and unrelated samples for genome-wide association studies‡

    PubMed Central

    Crossett, Andrew; Kent, Brian P.; Klei, Lambertus; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn; Devlin, Bernie

    2015-01-01

    We propose a method to analyze family-based samples together with unrelated cases and controls. The method builds on the idea of matched case–control analysis using conditional logistic regression (CLR). For each trio within the family, a case (the proband) and matched pseudo-controls are constructed, based upon the transmitted and untransmitted alleles. Unrelated controls, matched by genetic ancestry, supplement the sample of pseudo-controls; likewise unrelated cases are also paired with genetically matched controls. Within each matched stratum, the case genotype is contrasted with control pseudo-control genotypes via CLR, using a method we call matched-CLR (mCLR). Eigenanalysis of numerous SNP genotypes provides a tool for mapping genetic ancestry. The result of such an analysis can be thought of as a multidimensional map, or eigenmap, in which the relative genetic similarities and differences amongst individuals is encoded in the map. Once constructed, new individuals can be projected onto the ancestry map based on their genotypes. Successful differentiation of individuals of distinct ancestry depends on having a diverse, yet representative sample from which to construct the ancestry map. Once samples are well-matched, mCLR yields comparable power to competing methods while ensuring excellent control over Type I error. PMID:20862653

  7. Tracing Cattle Breeds with Principal Components Analysis Ancestry Informative SNPs

    PubMed Central

    Lewis, Jamey; Abas, Zafiris; Dadousis, Christos; Lykidis, Dimitrios; Paschou, Peristera; Drineas, Petros

    2011-01-01

    The recent release of the Bovine HapMap dataset represents the most detailed survey of bovine genetic diversity to date, providing an important resource for the design and development of livestock production. We studied this dataset, comprising more than 30,000 Single Nucleotide Polymorphisms (SNPs) for 19 breeds (13 taurine, three zebu, and three hybrid breeds), seeking to identify small panels of genetic markers that can be used to trace the breed of unknown cattle samples. Taking advantage of the power of Principal Components Analysis and algorithms that we have recently described for the selection of Ancestry Informative Markers from genomewide datasets, we present a decision-tree which can be used to accurately infer the origin of individual cattle. In doing so, we present a thorough examination of population genetic structure in modern bovine breeds. Performing extensive cross-validation experiments, we demonstrate that 250-500 carefully selected SNPs suffice in order to achieve close to 100% prediction accuracy of individual ancestry, when this particular set of 19 breeds is considered. Our methods, coupled with the dense genotypic data that is becoming increasingly available, have the potential to become a valuable tool and have considerable impact in worldwide livestock production. They can be used to inform the design of studies of the genetic basis of economically important traits in cattle, as well as breeding programs and efforts to conserve biodiversity. Furthermore, the SNPs that we have identified can provide a reliable solution for the traceability of breed-specific branded products. PMID:21490966

  8. Asians demonstrate reduced sensitivity to unpredictable threat: a preliminary startle investigation using genetic ancestry in a multiethnic sample.

    PubMed

    Nelson, Brady D; Bishop, Jeffrey R; Sarapas, Casey; Kittles, Rick A; Shankman, Stewart A

    2014-06-01

    Research has indicated that individuals of Asian descent, relative to other racial groups, demonstrate reduced emotional responding and lower prevalence rates of several anxiety disorders. It is unclear though whether these group differences extend to biomarkers of anxiety disorders and whether genetic differences play a role. This study compared self-identified Caucasian, Latino, and Asian persons (total N = 174) on startle response during a baseline period and while anticipating unpredictable threat-a putative biomarker for certain anxiety disorders--as well as predictable threat. In addition, the association between genetic ancestry and startle response was examined within each racial group to determine potential genetic influences on responding. For the baseline period, Asian participants exhibited a smaller startle response relative to Caucasian and Latino participants, who did not differ. Within each racial group, genetic ancestry was associated with baseline startle. Furthermore, genetic ancestry mediated racial group differences in baseline startle. For the threat conditions, a Race × Condition interaction indicated that Asian participants exhibited reduced startle potentiation to unpredictable, but not predicable, threat relative to Caucasian and Latino participants, who did not differ. However, genetic ancestry was not associated with threat-potentiated startle in any racial group. This study adds to the growing literature on racial differences in emotional responding and provides preliminary evidence suggesting that genetic ancestry may play an important role. Moreover, reduced sensitivity to unpredictable threat may reflect a mechanism for why individuals of Asian descent are at less risk for particular anxiety disorders relative to other racial groups.

  9. The association of individual and neighborhood social cohesion, stressors, and crime on smoking status among African-American women in southeastern US subsidized housing neighborhoods.

    PubMed

    Andrews, Jeannette O; Mueller, Martina; Newman, Susan D; Magwood, Gayenell; Ahluwalia, Jasjit S; White, Kellee; Tingen, Martha S

    2014-12-01

    The purpose of this study was to examine the associations between individual and neighborhood social contextual factors and smoking prevalence among African-American women in subsidized neighborhoods. We randomly sampled 663 adult women in 17 subsidized neighborhoods in two Southeastern US states. The smoking prevalence among participants was 37.6%, with an estimated neighborhood household prevalence ranging from 30 to 68%. Smokers were more likely to be older, have lower incomes, have lower BMI, and live with other smokers. Women with high social cohesion were less likely to smoke, although living in neighborhoods with higher social cohesion was not associated with smoking prevalence. Women with higher social cohesion were more likely to be older and had lived in the neighborhood longer. Women with high stress (related to violence and disorder) and who lived in neighborhoods with higher stress were more likely to smoke. Younger women were more likely to have higher stress than older women. There were no statistically significant associations with objective neighborhood crime data in any model. This is the first study to examine both individual and neighborhood social contextual correlates among African-American women in subsidized neighborhoods. This study extends findings about smoking behaviors and neighborhood social contexts in this high-risk, urban population. Future research is needed to explore age and residential stability differences and perceptions of social cohesion, neighborhood disorder, and perceived violence in subsidized housing. Further research is also warranted on African-American women, subsidized housing, smoking, social context, health disparities' effective strategies to address these individual and contextual factors to better inform future ecological-based multilevel prevention, and cessation intervention strategies.

  10. Do people from the Jewish community prefer ancestry-based or pan-ethnic expanded carrier screening?

    PubMed Central

    Holtkamp, Kim C A; van Maarle, Merel C; Schouten, Maria J E; Dondorp, Wybo J; Lakeman, Phillis; Henneman, Lidewij

    2016-01-01

    Ancestry-based carrier screening in the Ashkenazi Jewish population entails screening for specific autosomal recessive founder mutations, which are rarer among the general population. As it is now technically feasible to screen for many more diseases, the question arises whether this population prefers a limited ancestry-based offer or a pan-ethnic expanded carrier screening panel that goes beyond the diseases that are frequent in their own population, and is offered regardless of ancestry. An online questionnaire was completed by 145 individuals from the Dutch Jewish community (≥18 years) between April and July 2014. In total, 64.8% were aware of the existence of ancestry-based carrier screening, and respondents were generally positive about screening. About half (53.8%) preferred pan-ethnic expanded carrier screening, whereas 42.8% preferred ancestry-based screening. Reasons for preferring pan-ethnic screening included ‘everyone has a right to be tested', ‘fear of stigmatization when offering ancestry-based panels', and ‘difficulties with identifying risk owing to mixed backgrounds'. ‘Preventing high healthcare costs' was the most important reason against pan-ethnic carrier screening among those in favor of an ancestry-based panel. In conclusion, these findings show that people from the Dutch Jewish community have a positive attitude regarding carrier screening in their community for a wide range of diseases. As costs of expanded carrier screening panels are most likely to drop in the near future, it is expected that these panels will receive more support in the future. PMID:25966636

  11. Do people from the Jewish community prefer ancestry-based or pan-ethnic expanded carrier screening?

    PubMed

    Holtkamp, Kim C A; van Maarle, Merel C; Schouten, Maria J E; Dondorp, Wybo J; Lakeman, Phillis; Henneman, Lidewij

    2016-02-01

    Ancestry-based carrier screening in the Ashkenazi Jewish population entails screening for specific autosomal recessive founder mutations, which are rarer among the general population. As it is now technically feasible to screen for many more diseases, the question arises whether this population prefers a limited ancestry-based offer or a pan-ethnic expanded carrier screening panel that goes beyond the diseases that are frequent in their own population, and is offered regardless of ancestry. An online questionnaire was completed by 145 individuals from the Dutch Jewish community (≥ 18 years) between April and July 2014. In total, 64.8% were aware of the existence of ancestry-based carrier screening, and respondents were generally positive about screening. About half (53.8%) preferred pan-ethnic expanded carrier screening, whereas 42.8% preferred ancestry-based screening. Reasons for preferring pan-ethnic screening included 'everyone has a right to be tested', 'fear of stigmatization when offering ancestry-based panels', and 'difficulties with identifying risk owing to mixed backgrounds'. 'Preventing high healthcare costs' was the most important reason against pan-ethnic carrier screening among those in favor of an ancestry-based panel. In conclusion, these findings show that people from the Dutch Jewish community have a positive attitude regarding carrier screening in their community for a wide range of diseases. As costs of expanded carrier screening panels are most likely to drop in the near future, it is expected that these panels will receive more support in the future.

  12. Genetic Evidence of African Slavery at the Beginning of the Trans-Atlantic Slave Trade

    PubMed Central

    Martiniano, Rui; Coelho, Catarina; Ferreira, Maria Teresa; Neves, Maria João; Pinhasi, Ron; Bradley, Daniel G.

    2014-01-01

    An archaeological excavation in Valle da Gafaria (Lagos, Portugal), revealed two contiguous burial places outside the medieval city walls, dating from the 15th–17th centuries AD: one was interpreted as a Leprosarium cemetery and the second as an urban discard deposit, where signs of violent, unceremonious burials suggested that these remains may belong to slaves captured in Africa by the Portuguese. We obtained random short autosomal sequence reads from seven individuals: two from the latter site and five from the Leprosarium and used these to call SNP identities and estimate ancestral affinities with modern reference data. The Leprosarium site samples were less preserved but gave some probability of both African and European ancestry. The two discard deposit burials each gave African affinity signals, which were further refined toward modern West African or Bantu genotyped samples. These data from distressed burials illustrate an African contribution to a low status stratum of Lagos society at a time when this port became a hub of the European trade in African slaves which formed a precursor to the transatlantic transfer of millions. PMID:25104065

  13. Genetic evidence of African slavery at the beginning of the trans-Atlantic slave trade.

    PubMed

    Martiniano, Rui; Coelho, Catarina; Ferreira, Maria Teresa; Neves, Maria João; Pinhasi, Ron; Bradley, Daniel G

    2014-08-08

    An archaeological excavation in Valle da Gafaria (Lagos, Portugal), revealed two contiguous burial places outside the medieval city walls, dating from the 15(th)-17(th) centuries AD: one was interpreted as a Leprosarium cemetery and the second as an urban discard deposit, where signs of violent, unceremonious burials suggested that these remains may belong to slaves captured in Africa by the Portuguese. We obtained random short autosomal sequence reads from seven individuals: two from the latter site and five from the Leprosarium and used these to call SNP identities and estimate ancestral affinities with modern reference data. The Leprosarium site samples were less preserved but gave some probability of both African and European ancestry. The two discard deposit burials each gave African affinity signals, which were further refined toward modern West African or Bantu genotyped samples. These data from distressed burials illustrate an African contribution to a low status stratum of Lagos society at a time when this port became a hub of the European trade in African slaves which formed a precursor to the transatlantic transfer of millions.

  14. Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness.

    PubMed

    Conomos, Matthew P; Miller, Michael B; Thornton, Timothy A

    2015-05-01

    Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multidimensional scaling (MDS), and model-based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC-AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC-AiR utilizes genome-screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC-AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC-AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC-AiR provides better prediction of ancestry in a variety of structure settings than using 10 (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC-AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness.

  15. The Astrobiological Case for Our Cosmic Ancestry

    NASA Astrophysics Data System (ADS)

    Wickramasinghe, Chandra

    With steadily mounting evidence that points to a cosmic origin of terrestrial life, a cultural barrier prevails against admitting that such a connection exists. Astronomy continues to reveal the presence of organic molecules and organic dust on a huge cosmic scale, amounting to a third of interstellar carbon tied up in this form. Just as the overwhelming bulk of organics on Earth stored over geological timescales are derived from the degradation of living cells, so it seems most likely that interstellar organics in large measure also derive from biology. As we enter a new decade -- the year 2010 -- a clear pronouncement of our likely alien ancestry and of the existence of extraterrestrial life on a cosmic scale would seem to be overdue.

  16. The astrobiological case for our cosmic ancestry

    NASA Astrophysics Data System (ADS)

    Wickramasinghe, Chandra

    2010-04-01

    With steadily mounting evidence that points to a cosmic origin of terrestrial life, a cultural barrier prevails against admitting that such a connection exists. Astronomy continues to reveal the presence of organic molecules and organic dust on a huge cosmic scale, amounting to a third of interstellar carbon tied up in this form. Just as the overwhelming bulk of organics on Earth stored over geological timescales are derived from the degradation of living cells, so it seems likely that interstellar organics in large measure also derive from biology. As we enter a new decade - the year 2010 - a clear pronouncement of our likely alien ancestry and of the existence of extraterrestrial life on a cosmic scale would seem to be overdue.

  17. Soft tissue thickness values for black and coloured South African children aged 6-13 years.

    PubMed

    Briers, N; Briers, T M; Becker, P J; Steyn, M

    2015-07-01

    In children, craniofacial changes due to facial growth complicate facial approximations and require specific knowledge of soft tissue thicknesses (STT). The lack of South African juvenile STT standards of particular age groups, sex and ancestry is problematic. According to forensic artists in the South African Police Service the use of African-American values to reconstruct faces of Black South African children yields poor results. In order to perform a facial approximation that presents a true reflection of the child in question, information regarding differences in facial soft tissue at different ages, sexes and ancestry groups is needed. The aims of this study were to provide data on STT of South African Black and Coloured children and to assess differences in STT with respect to age, sex and ancestry. STT was measured using cephalograms of South African children (n=388), aged 6-13 years. After digitizing the images, STT measurements were taken at ten mid-facial landmarks from each image using the iTEM measuring program. STT comparisons between groups per age, sex and ancestry were statistically analyzed. The results showed that STT differences at lower face landmarks are more pronounced in age groups per ancestry as opposed to differences per age and sex. Generally, an increase in STT was seen between 6-10 year old groups and 11-13 year old groups, regardless of ancestry and sex, at the midphiltrum, labiale inferius, pogonion, and beneath chin landmarks. This research created a reference dataset for STT of South African children of Black and Coloured ancestry per age and sex that will be useful for facial reconstruction/approximation of juvenile remains.

  18. Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B-cell acute lymphoblastic leukemia.

    PubMed

    Walsh, Kyle M; de Smith, Adam J; Welch, Tara C; Smirnov, Ivan; Cunningham, Marc J; Ma, Xiaomei; Chokkalingam, Anand P; Dahl, Gary V; Roberts, William; Barcellos, Lisa F; Buffler, Patricia A; Metayer, Catherine; Wiemels, Joseph L

    2014-07-01

    Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) than non-Hispanic whites but tend to be diagnosed at older ages. In genome-wide association studies, Native American ancestry and polymorphisms in six genes have been associated with ALL risk. In multivariable regression models, we investigated whether genomic ancestry, inherited risk SNPs, or acquired somatic alterations were associated with differences in age at diagnosis in Hispanic children with B-cell ALL. Genome-wide array data were used to estimate each participant's percent membership in the three Hispanic ancestral populations: Native American, African, and European. Each 20% increase in European ancestry was associated with a six month younger age at diagnosis (95% CI = 0.36-11.6 months, P = 0.037). Correspondingly, each 20% increase in Native American ancestry was associated with a six-month older age at diagnosis (P = 0.037). Both the TEL-AML1 translocation and high-hyperdiploidy were associated with younger age at diagnosis (24.4 months, P = 2.0 x 10(-4) and 12.4 months, P = 0.011, respectively), while CDKN2A and IKZF1 deletions were associated with older age at diagnosis (19.7 months, P = 7.0 x 10(-4) and 18.1 months, P = 0.012, respectively). No associations with age at diagnosis were observed for RAS mutation, PAX5 deletion or for known heritable risk alleles in IKZF1, CDKN2A, PIP4K2A, GATA3, ARID5B, or CEBPE. Because younger age at diagnosis is associated with improved treatment outcomes for children with ALL, the effect of European ancestry on ALL survival may be mediated by its effect on age at diagnosis, or by proxy, its association with more treatable molecular subtypes of ALL.

  19. The genetics of East African populations: a Nilo-Saharan component in the African genetic landscape

    PubMed Central

    Dobon, Begoña; Hassan, Hisham Y.; Laayouni, Hafid; Luisi, Pierre; Ricaño-Ponce, Isis; Zhernakova, Alexandra; Wijmenga, Cisca; Tahir, Hanan; Comas, David; Netea, Mihai G.; Bertranpetit, Jaume

    2015-01-01

    East Africa is a strategic region to study human genetic diversity due to the presence of ethnically, linguistically, and geographically diverse populations. Here, we provide new insight into the genetic history of populations living in the Sudanese region of East Africa by analysing nine ethnic groups belonging to three African linguistic families: Niger-Kordofanian, Nilo-Saharan and Afro-Asiatic. A total of 500 individuals were genotyped for 200,000 single-nucleotide polymorphisms. Principal component analysis, clustering analysis using ADMIXTURE, FST statistics, and the three-population test were used to investigate the underlying genetic structure and ancestry of the different ethno-linguistic groups. Our analyses revealed a genetic component for Sudanese Nilo-Saharan speaking groups (Darfurians and part of Nuba populations) related to Nilotes of South Sudan, but not to other Sudanese populations or other sub-Saharan populations. Populations inhabiting the North of the region showed close genetic affinities with North Africa, with a component that could be remnant of North Africans before the migrations of Arabs from Arabia. In addition, we found very low genetic distances between populations in genes important for anti-malarial and anti-bacterial host defence, suggesting similar selective pressures on these genes and stressing the importance of considering functional pathways to understand the evolutionary history of populations. PMID:26017457

  20. Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and Caucasian Americans

    DTIC Science & Technology

    2015-10-01

    It is anticipated that molecular determinants of aggressive prostate cancer in African American men, including somatic mutations and SNPs associated...molecular stratification, germline variants (SNPs), admixture mapping, European and African ancestry, somatic mutations, aggressive cancer... aggressive CaP in AA men include somatic mutations (TMPRSS2-ERG) and germline variants (SNPs). The objective will be achieved by the following specific

  1. Y chromosome haplogroups and prostate cancer in populations of European and Ashkenazi Jewish ancestry.

    PubMed

    Wang, Zhaoming; Parikh, Hemang; Jia, Jinping; Myers, Timothy; Yeager, Meredith; Jacobs, Kevin B; Hutchinson, Amy; Burdett, Laurie; Ghosh, Arpita; Thun, Michael J; Gapstur, Susan M; Ryan Diver, W; Virtamo, Jarmo; Albanes, Demetrius; Cancel-Tassin, Geraldine; Valeri, Antoine; Cussenot, Olivier; Offit, Kenneth; Giovannucci, Ed; Ma, Jing; Stampfer, Meir J; Michael Gaziano, J; Hunter, David J; Dutra-Clarke, Ana; Kirchhoff, Tomas; Alavanja, Michael; Freeman, Laura B; Koutros, Stella; Hoover, Robert; Berndt, Sonja I; Hayes, Richard B; Agalliu, Ilir; Burk, Robert D; Wacholder, Sholom; Thomas, Gilles; Amundadottir, Laufey

    2012-07-01

    Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P(meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P(meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.

  2. Y Chromosome Lineages in Men of West African Descent

    PubMed Central

    Keita, Shomarka O. Y.; Kittles, Rick A.

    2012-01-01

    The early African experience in the Americas is marked by the transatlantic slave trade from ∼1619 to 1850 and the rise of the plantation system. The origins of enslaved Africans were largely dependent on European preferences as well as the availability of potential laborers within Africa. Rice production was a key industry of many colonial South Carolina low country plantations. Accordingly, rice plantations owners within South Carolina often requested enslaved Africans from the so-called “Grain Coast” of western Africa (Senegal to Sierra Leone). Studies on the African origins of the enslaved within other regions of the Americas have been limited. To address the issue of origins of people of African descent within the Americas and understand more about the genetic heterogeneity present within Africa and the African Diaspora, we typed Y chromosome specific markers in 1,319 men consisting of 508 west and central Africans (from 12 populations), 188 Caribbeans (from 2 islands), 532 African Americans (AAs from Washington, DC and Columbia, SC), and 91 European Americans. Principal component and admixture analyses provide support for significant Grain Coast ancestry among African American men in South Carolina. AA men from DC and the Caribbean showed a closer affinity to populations from the Bight of Biafra. Furthermore, 30–40% of the paternal lineages in African descent populations in the Americas are of European ancestry. Diverse west African ancestries and sex-biased gene flow from EAs has contributed greatly to the genetic heterogeneity of African populations throughout the Americas and has significant implications for gene mapping efforts in these populations. PMID:22295064

  3. Question-Asking and Advocacy by African American Parents at Individualized Education Program Meetings: A Social and Cultural Capital Perspective

    ERIC Educational Resources Information Center

    Wilson, Natasha M.

    2015-01-01

    The Individuals with Disabilities Education Improvement Act of 2004 mandates parental involvement during Individualized Education Program (IEP) meetings. Several factors including previous IEP experiences, level of ongoing communication between parents and education professionals, or existence of social and cultural capital resources can impact…

  4. Fast spatial ancestry via flexible allele frequency surfaces

    PubMed Central

    Rañola, John Michael; Novembre, John; Lange, Kenneth

    2014-01-01

    Motivation: Unique modeling and computational challenges arise in locating the geographic origin of individuals based on their genetic backgrounds. Single-nucleotide polymorphisms (SNPs) vary widely in informativeness, allele frequencies change non-linearly with geography and reliable localization requires evidence to be integrated across a multitude of SNPs. These problems become even more acute for individuals of mixed ancestry. It is hardly surprising that matching genetic models to computational constraints has limited the development of methods for estimating geographic origins. We attack these related problems by borrowing ideas from image processing and optimization theory. Our proposed model divides the region of interest into pixels and operates SNP by SNP. We estimate allele frequencies across the landscape by maximizing a product of binomial likelihoods penalized by nearest neighbor interactions. Penalization smooths allele frequency estimates and promotes estimation at pixels with no data. Maximization is accomplished by a minorize–maximize (MM) algorithm. Once allele frequency surfaces are available, one can apply Bayes’ rule to compute the posterior probability that each pixel is the pixel of origin of a given person. Placement of admixed individuals on the landscape is more complicated and requires estimation of the fractional contribution of each pixel to a person’s genome. This estimation problem also succumbs to a penalized MM algorithm. Results: We applied the model to the Population Reference Sample (POPRES) data. The model gives better localization for both unmixed and admixed individuals than existing methods despite using just a small fraction of the available SNPs. Computing times are comparable with the best competing software. Availability and implementation: Software will be freely available as the OriGen package in R. Contact: ranolaj@uw.edu or klange@ucla.edu Supplementary information: Supplementary data are available at

  5. Functional Significance of Single Nucleotide Polymorphisms in the Lactase Gene in Diverse United States Subjects and Evidence for a Novel Lactase Persistence Allele at -13909 in Those of European Ancestry

    PubMed Central

    Baffour-Awuah, Nana Yaa; Fleet, Sarah; Baker, Susan S.; Butler, Johannah L.; Campbell, Catarina; Tischfield, Samuel; Mitchell, Paul D.; Moon, Jennifer E.; Allende-Richter, Sophie; Fishman, Laurie; Bousvaros, Athos; Fox, Victor; Kuokkanen, Mikko; Montgomery, Robert K.; Grand, Richard J.; Hirschhorn, Joel N.

    2014-01-01

    Objectives Recent data from mainly homogeneous European and African populations implicate a 140 bp region 5′ to the transcriptional start site of LCT (the lactase gene) as a regulatory site for lactase persistence and non-persistence. As there are no studies of United States non-homogeneous populations, we performed genotype/phenotype analysis of the -13910 and -22018 LCT SNPs in New England children, mostly of European ancestry. Methods Duodenal biopsies were processed for disaccharidase activities, RNA quantification by RT-PCR, allelic expression ratios by PCR, and genotyping and SNP analysis. Results were compared to clinical information. Results Lactase activity and mRNA levels, as well as sucrase-to-lactase ratios of enzyme activity and mRNA, showed robust correlations with genotype. None of the other LCT SNPs showed as strong a correlation with enzyme or mRNA activities as did -13910. Data were consistent with the -13910 being the causal sequence variant rather than -22018. Four individuals heterozygous for -13910T/C had allelic expression patterns similar to individuals with -13910C/C genotypes; of these, 2 showed equal LCT expression from the 2 alleles and a novel variant (-13909C>A) associated with lactase persistence. Conclusion The identification of -13910C/C genotype is very likely to predict lactase non-persistence, consistent with prior published studies. A -13910T/T genotype will frequently, but not perfectly, predict lactase persistence in this mixed European-ancestry population; a -13910T/C genotype will not predict the phenotype. A long, rare haplotype in 2 individuals with -13910T/C genotype but equal allele-specific expression contains a novel lactase persistence allele present at -13909. PMID:25625576

  6. Ancestry Testing and the Practice of Genetic Counseling.

    PubMed

    Kirkpatrick, Brianne E; Rashkin, Misha D

    2017-02-01

    Ancestry testing is a home DNA test with many dimensions; in some cases, the implications and outcomes of testing cross over into the health sphere. Common reasons for seeking ancestry testing include determining an estimate of customer's ethnic background, identifying genetic relatives, and securing a raw DNA data file that can be used for other purposes. As the ancestry test marketplace continues to grow, and third-party vendors empower the general public to analyze their own genetic material, the role of the genetic counselor is likely to evolve dramatically. Roles of the genetic counselor may include assisting clients with the interpretation of and adaptation to these results, as well as advising the companies involved in this sector on the ethical, legal, and social issues associated with testing. This paper reviews the history, fundamentals, intended uses, and unintended consequences of ancestry genetic testing. It also discusses the types of information in an ancestry testing result, situations that might involve a clinical genetic counselor, and the benefits, limitations, and functions that ancestry genetic testing can play in a clinical genetics setting.

  7. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans.

    PubMed

    Raghavan, Maanasa; Skoglund, Pontus; Graf, Kelly E; Metspalu, Mait; Albrechtsen, Anders; Moltke, Ida; Rasmussen, Simon; Stafford, Thomas W; Orlando, Ludovic; Metspalu, Ene; Karmin, Monika; Tambets, Kristiina; Rootsi, Siiri; Mägi, Reedik; Campos, Paula F; Balanovska, Elena; Balanovsky, Oleg; Khusnutdinova, Elza; Litvinov, Sergey; Osipova, Ludmila P; Fedorova, Sardana A; Voevoda, Mikhail I; DeGiorgio, Michael; Sicheritz-Ponten, Thomas; Brunak, Søren; Demeshchenko, Svetlana; Kivisild, Toomas; Villems, Richard; Nielsen, Rasmus; Jakobsson, Mattias; Willerslev, Eske

    2014-01-02

    The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians, there is no consensus with regard to which specific Old World populations they are closest to. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native

  8. Explaining the visible and the invisible: Public knowledge of genetics, ancestry, physical appearance and race in Colombia.

    PubMed

    Schwartz-Marín, Ernesto; Wade, Peter

    2015-12-01

    Using data from focus groups conducted in Colombia, we explore how educated lay audiences faced with scenarios about ancestry and genetics draw on widespread and dominant notions of nation, race and belonging in Colombia to ascribe ancestry to collectivities and to themselves as individuals. People from a life sciences background tend to deploy idioms of race and genetics more readily than people from a humanities and race-critical background. When they considered individuals, people tempered or domesticated the more mechanistic explanations about racialized physical appearance, ancestry and genetics that were apparent at the collective level. Ideas of the latency and manifestation of invisible traits were an aspect of this domestication. People ceded ultimate authority to genetic science, but deployed it to work alongside what they already knew. Notions of genetic essentialism co-exist with the strategic use of genetic ancestry in ways that both fix and unfix race. Our data indicate the importance of attending to the different epistemological stances through which people define authoritative knowledge and to the importance of distinguishing the scale of resolution at which the question of diversity is being posed.

  9. Explaining the visible and the invisible: Public knowledge of genetics, ancestry, physical appearance and race in Colombia

    PubMed Central

    Schwartz-Marín, Ernesto; Wade, Peter

    2015-01-01

    Using data from focus groups conducted in Colombia, we explore how educated lay audiences faced with scenarios about ancestry and genetics draw on widespread and dominant notions of nation, race and belonging in Colombia to ascribe ancestry to collectivities and to themselves as individuals. People from a life sciences background tend to deploy idioms of race and genetics more readily than people from a humanities and race-critical background. When they considered individuals, people tempered or domesticated the more mechanistic explanations about racialized physical appearance, ancestry and genetics that were apparent at the collective level. Ideas of the latency and manifestation of invisible traits were an aspect of this domestication. People ceded ultimate authority to genetic science, but deployed it to work alongside what they already knew. Notions of genetic essentialism co-exist with the strategic use of genetic ancestry in ways that both fix and unfix race. Our data indicate the importance of attending to the different epistemological stances through which people define authoritative knowledge and to the importance of distinguishing the scale of resolution at which the question of diversity is being posed. PMID:27480001

  10. Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a South American population isolate.

    PubMed

    Bedoya, Gabriel; Montoya, Patricia; García, Jenny; Soto, Ivan; Bourgeois, Stephane; Carvajal, Luis; Labuda, Damian; Alvarez, Victor; Ospina, Jorge; Hedrick, Philip W; Ruiz-Linares, Andrés

    2006-05-09

    Although it is well established that Hispanics generally have a mixed Native American, African, and European ancestry, the dynamics of admixture at the foundation of Hispanic populations is heterogeneous and poorly documented. Genetic analyses are potentially very informative for probing the early demographic history of these populations. Here we evaluate the genetic structure and admixture dynamics of a province in northwest Colombia (Antioquia), which prior analyses indicate was founded mostly by Spanish men and native women. We examined surname, Y chromosome, and mtDNA diversity in a geographically structured sample of the region and obtained admixture estimates with highly informative autosomal and X chromosome markers. We found evidence of reduced surname diversity and support for the introduction of several common surnames by single founders, consistent with the isolation of Antioquia after the colonial period. Y chromosome and mtDNA data indicate little population substructure among founder Antioquian municipalities. Interestingly, despite a nearly complete Native American mtDNA background, Antioquia has a markedly predominant European ancestry at the autosomal and X chromosome level, which suggests that, after foundation, continuing admixture with Spanish men (but not with native women) increased the European nuclear ancestry of Antioquia. This scenario is consistent with historical information and with results from population genetics theory.

  11. Admixture dynamics in Hispanics: A shift in the nuclear genetic ancestry of a South American population isolate

    PubMed Central

    Bedoya, Gabriel; Montoya, Patricia; García, Jenny; Soto, Ivan; Bourgeois, Stephane; Carvajal, Luis; Labuda, Damian; Alvarez, Victor; Ospina, Jorge; Hedrick, Philip W.; Ruiz-Linares, Andrés

    2006-01-01

    Although it is well established that Hispanics generally have a mixed Native American, African, and European ancestry, the dynamics of admixture at the foundation of Hispanic populations is heterogeneous and poorly documented. Genetic analyses are potentially very informative for probing the early demographic history of these populations. Here we evaluate the genetic structure and admixture dynamics of a province in northwest Colombia (Antioquia), which prior analyses indicate was founded mostly by Spanish men and native women. We examined surname, Y chromosome, and mtDNA diversity in a geographically structured sample of the region and obtained admixture estimates with highly informative autosomal and X chromosome markers. We found evidence of reduced surname diversity and support for the introduction of several common surnames by single founders, consistent with the isolation of Antioquia after the colonial period. Y chromosome and mtDNA data indicate little population substructure among founder Antioquian municipalities. Interestingly, despite a nearly complete Native American mtDNA background, Antioquia has a markedly predominant European ancestry at the autosomal and X chromosome level, which suggests that, after foundation, continuing admixture with Spanish men (but not with native women) increased the European nuclear ancestry of Antioquia. This scenario is consistent with historical information and with results from population genetics theory. PMID:16648268

  12. Higher levels of neanderthal ancestry in East Asians than in Europeans.

    PubMed

    Wall, Jeffrey D; Yang, Melinda A; Jay, Flora; Kim, Sung K; Durand, Eric Y; Stevison, Laurie S; Gignoux, Christopher; Woerner, August; Hammer, Michael F; Slatkin, Montgomery

    2013-05-01

    Neanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from ∼30,000 to 300,000 years ago (KYA). They coexisted with modern humans during part of this time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1-4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50-80 KYA. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal-modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations.

  13. Polygenic risk assessment reveals pleiotropy between sarcoidosis and inflammatory disorders in the context of genetic ancestry.

    PubMed

    Lareau, C A; DeWeese, C F; Adrianto, I; Lessard, C J; Gaffney, P M; Iannuzzi, M C; Rybicki, B A; Levin, A M; Montgomery, C G

    2017-03-09

    Sarcoidosis is a complex disease of unknown etiology characterized by the presence of granulomatous inflammation. Though various immune system pathways have been implicated in disease, the relationship between the genetic determinants of sarcoidosis and other inflammatory disorders has not been characterized. Herein, we examined the degree of genetic pleiotropy common to sarcoidosis and other inflammatory disorders to identify shared pathways and disease systems pertinent to sarcoidosis onset. To achieve this, we quantify the association of common variant polygenic risk scores from nine complex inflammatory disorders with sarcoidosis risk. Enrichment analyses of genes implicated in pleiotropic associations were further used to elucidate candidate pathways. In European-Americans, we identify significant pleiotropy between risk of sarcoidosis and risk of asthma (R(2)=2.03%; P=8.89 × 10(-9)), celiac disease (R(2)=2.03%; P=8.21 × 10(-9)), primary biliary cirrhosis (R(2)=2.43%; P=2.01 × 10(-10)) and rheumatoid arthritis (R(2)=4.32%; P=2.50 × 10(-17)). These associations validate in African Americans only after accounting for the proportion of genome-wide European ancestry, where we demonstrate similar effects of polygenic risk for African-Americans with the highest levels of European ancestry. Variants and genes implicated in European-American pleiotropic associations were enriched for pathways involving interleukin-12, interleukin-27 and cell adhesion molecules, corroborating the hypothesized immunopathogenesis of disease.Genes and Immunity advance online publication, 9 March 2017; doi:10.1038/gene.2017.3.

  14. Genomic Variation of Inbreeding and Ancestry in the Remaining Two Isle Royale Wolves.

    PubMed

    Hedrick, Philip W; Kardos, Marty; Peterson, Rolf O; Vucetich, John A

    2016-12-11

    Inbreeding, relatedness, and ancestry have traditionally been estimated with pedigree information, however, molecular genomic data can provide more detailed examination of these properties. For example, pedigree information provides estimation of the expected value of these measures but molecular genomic data can estimate the realized values of these measures in individuals. Here, we generate the theoretical distribution of inbreeding, relatedness, and ancestry for the individuals in the pedigree of the Isle Royale wolves, the first examination of such variation in a wild population with a known pedigree. We use the 38 autosomes of the dog genome and their estimated map lengths in our genomic analysis. Although it is known that the remaining wolves are highly inbred, closely related, and descend from only 3 ancestors, our analyses suggest that there is significant variation in the realized inbreeding and relatedness around pedigree expectations. For example, the expected inbreeding in a hypothetical offspring from the 2 remaining wolves is 0.438 but the realized 95% genomic confidence interval is from 0.311 to 0.565. For individual chromosomes, a substantial proportion of the whole chromosomes are completely identical by descent. This examination provides a background to use when analyzing molecular genomic data for individual levels of inbreeding, relatedness, and ancestry. The level of variation in these measures is a function of the time to the common ancestor(s), the number of chromosomes, and the rate of recombination. In the Isle Royale wolf population, the few generations to a common ancestor results in the high variance in genomic inbreeding.

  15. Knowledge, attitudes and practices of South African healthcare workers regarding the prevention and treatment of influenza among HIV-infected individuals

    PubMed Central

    Gaga, Sisanda; Clark, David; Muller, Madeleine; Kuwane, Bulenani; Cohen, Cheryl; Walaza, Sibongile; Tempia, Stefano; Ramatoboe, Puleng; Furumele, Tsakani; Widdowson, Marc-Alain; McMorrow, Meredith L.; Cohen, Adam L.

    2017-01-01

    Background The South African Department of Health (DOH) publishes annual guidelines identifying priority groups, including immunosuppressed individuals and healthcare workers (HCW), for influenza vaccination and treatment. How these guidelines have impacted HCW and their patients, particularly those infected with HIV, remains unknown. Methods We aimed to describe the knowledge, attitudes and practices regarding influenza and the vaccine among South African HCW. Surveys were distributed by two local non-governmental organizations in public health clinics and hospitals in 21 districts/municipalities (5 of 9 provinces). Results There were 1164 respondents; median age 41 years; 978/1126 (87%) female; 801/1122 (71%) nurses. One-third (34%) of HCW reported getting influenza vaccine 2013/2014 and most (94%) recommended influenza vaccine to patients infected with HIV. Ability to get vaccine free of charge (aOR 1.69; 95% CI 1.21–2.37) and having received influenza government training (aOR 1.50; 95% CI 1.04–2.15) were significantly associated with self-reported vaccination in 2013/2014. Self-reported 2013/2014 vaccination (aOR 3.76; 95% CI 1.28–11.03) and availability of influenza vaccine during the healthcare visit (aOR 2.56; 95% CI 1.18–5.57) were significantly associated with recommending influenza vaccine to patients infected with HIV/AIDS. Conclusion Only one-third of participants were vaccinated in 2013–2014 but those who were vaccinated were more likely to recommend vaccination to their patients. Free and close access to influenza vaccine were associated with a higher likelihood of getting vaccinated in 2013/2014. HCW who reported getting the influenza vaccine themselves, had vaccine to offer during the patient consult and were familiar with DOH guidelines/trainings were more likely to recommend vaccine to HIV-infected patients. PMID:28301593

  16. The Ancestry and Affiliations of Kennewick Man

    PubMed Central

    Rasmussen, Morten; Poznik, G. David; Zollikofer, Christoph P. E.; de León, Marcia Ponce; Allentoft, Morten E.; Moltke, Ida; Jónsson, Hákon; Valdiosera, Cristina; Malhi, Ripan S.; Orlando, Ludovic; Bustamante, Carlos D.; Stafford, Thomas W.; Meltzer, David J.; Nielsen, Rasmus; Willerslev, Eske

    2016-01-01

    Kennewick Man, referred to as the Ancient One by Native Americans, is a male human skeleton discovered in Washington state (USA) in 1996 and initially radiocarbon-dated to 8340–9200 calibrated years BP1. His population affinities have been the subject of scientific debate and legal controversy. Based on initial study of cranial morphology it was asserted that Kennewick Man was neither Native American nor closely related to the Claimant Plateau tribes of the Pacific Northwest, who claimed ancestral relationship and requested repatriation under the Native American Graves Protection and Repatriation Act (NAGPRA). The morphological analysis was important to judicial decisions that Kennewick Man was not Native American and that therefore NAGPRA did not apply. Instead of repatriation, additional studies of the remains were permitted2. Subsequent craniometric analysis affirmed Kennewick Man to be more closely related to circumpacific groups such as the Ainu and Polynesians than he is to modern Native Americans2. In order to resolve Kennewick Man’s ancestry and affiliations, we have sequenced his genome to ~1× coverage and compared it to worldwide genomic data including the Ainu and Polynesians. We find that Kennewick Man is closer to modern Native Americans than to any other population worldwide. Among the Native American groups for whom genome wide data is available for comparison, several appear to be descended from a population closely related to that of Kennewick Man, including the Confederated Tribes of the Colville Reservation (Colville), one of the five tribes claiming Kennewick Man. We revisit the cranial analyses and find that, as opposed to genomic-wide comparisons, it is not possible on that basis to affiliate Kennewick Man to specific contemporary groups. We therefore conclude based on genetic comparisons that Kennewick Man shows continuity with Native North Americans over at least the last eight millennia. PMID:26087396

  17. Glucose intolerance in the West African Diaspora: a skeletal muscle fibre type distribution hypothesis.

    PubMed

    Nielsen, J; Christensen, D L

    2011-08-01

    In the United States, Black Americans are largely descendants of West African slaves; they have a higher relative proportion of obesity and experience a higher prevalence of diabetes than White Americans. However, obesity rates alone cannot explain the higher prevalence of type 2 diabetes. Type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. We hypothesize that the higher prevalence of type 2 diabetes in African Americans (as compared to White Americans) is facilitated by an inherited higher percentage of skeletal muscle fibre type II and a lower percentage of skeletal muscle fibre type I. Skeletal muscle fibre type II is less oxidative and more glycolytic than skeletal muscle fibre type I. Lower oxidative capacity is associated with lower fat oxidation and a higher disposal of lipids, which are stored as muscular adipose tissue in higher amounts in Black compared to White Americans. In physically active individuals, the influence of muscle fibre composition will not be as detrimental as in physically inactive individuals. This discrepancy is caused by the plasticity in the skeletal muscle fibre characteristics towards a higher activity of oxidative enzymes as a consequence of physical activity. We suggest that a higher percentage of skeletal muscle fibre type II combined with physical inactivity has an impact on insulin sensitivity and high prevalence of type 2 diabetes in Blacks of West African ancestry.

  18. Polymorphism of the human factor H-related gene (FHR-1) and of factor H in a West African individual

    SciTech Connect

    Meyer, C.G.; Skerka, C.; Zipfel, P.F.

    1995-03-01

    The human factor H-related 1 (FHR-1) protein is structurally and immunogenically related to the regulatory complement protein factor H (FH). Polymorphism of the FHR-1 gene is indicated by the nucleotide differences as described by the five cDNA clones isolated so far. In order to further analyze this polymorphism we identified PCR-primers which allow the simultaneous amplification of FHR-1 and FH alleles in a single polymerase chain reaction (PCR). By DNA sequence analysis, two novel FHR-1 variants and one as yet unrecognized FH allele could be characterized in an individual from Benin, West Africa. 2 refs., 1 fig.

  19. FH Tulsa-1 and -2: Two unique alleles for familial hypercholesterolemia presenting in an affected two-year-old African-American male

    SciTech Connect

    Blackett, P.R.; Altmiller, D.H.; Jelley, D.; Wilson, D.P.

    1995-11-20

    A two-year-old African American boy presented with cutaneous xanthomata and extreme hypercholesterolemia. Subsequent studies revealed that the LDL-cholesterol was 1,001 mg/dl and apoB 507 mg/dl. LDL-receptor activity was almost undetectable, which is compatible with the finding of two newly described defective alleles on exon 4 of the LDL-receptor gene coding for part of the ligand-binding domain. One allele contained a 21 base-pair insertion from codon 200 to 207 whereas the other had a point mutation at codon 207. The rarity of genes for FH reported in individuals of African ancestry is discussed. 16 refs., 2 figs., 2 tabs.

  20. Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study.

    PubMed

    Carlson, Christopher S; Matise, Tara C; North, Kari E; Haiman, Christopher A; Fesinmeyer, Megan D; Buyske, Steven; Schumacher, Fredrick R; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D; Duggan, David J; Spencer, Kylee L; Dumitrescu, Logan; Eaton, Charles B; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C; Hindorff, Lucia A; Kooperberg, Charles L

    2013-09-01

    The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification

  1. Genetically determined ancestry is more informative than self-reported race in HIV-infected and -exposed children

    PubMed Central

    Spector, Stephen A.; Brummel, Sean S.; Nievergelt, Caroline M.; Maihofer, Adam X.; Singh, Kumud K.; Purswani, Murli U.; Williams, Paige L.; Hazra, Rohan; Van Dyke, Russell; Seage, George R.

    2016-01-01

    Abstract The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants. In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined. According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian. GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes. PMID:27603370

  2. Genome-wide Scan of 29,141 African Americans Finds No Evidence of Directional Selection since Admixture

    PubMed Central

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Caporaso, Neil; Casey, Graham; Deming, Sandra L.; Diver, W. Ryan; Gapstur, Susan M.; Gillanders, Elizabeth M.; Harris, Curtis C.; Henderson, Brian E.; Ingles, Sue A.; Isaacs, William; De Jager, Phillip L.; John, Esther M.; Kittles, Rick A.; Larkin, Emma; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Tucker, Margaret A.; Wiencke, John K.; Witte, John S.; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Chanock, Stephen J.; Haiman, Christopher A.; Reich, David; Price, Alkes L.

    2014-01-01

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study’s conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas. PMID:25242497

  3. Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture.

    PubMed

    Bhatia, Gaurav; Tandon, Arti; Patterson, Nick; Aldrich, Melinda C; Ambrosone, Christine B; Amos, Christopher; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bock, Cathryn H; Caporaso, Neil; Casey, Graham; Deming, Sandra L; Diver, W Ryan; Gapstur, Susan M; Gillanders, Elizabeth M; Harris, Curtis C; Henderson, Brian E; Ingles, Sue A; Isaacs, William; De Jager, Phillip L; John, Esther M; Kittles, Rick A; Larkin, Emma; McNeill, Lorna H; Millikan, Robert C; Murphy, Adam; Neslund-Dudas, Christine; Nyante, Sarah; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret; Strom, Sara S; Tucker, Margaret A; Wiencke, John K; Witte, John S; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A; Zheng, Wei; Ziegler, Regina G; Chanock, Stephen J; Haiman, Christopher A; Reich, David; Price, Alkes L

    2014-10-02

    The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.

  4. The history of African gene flow into Southern Europeans, Levantines, and Jews.

    PubMed

    Moorjani, Priya; Patterson, Nick; Hirschhorn, Joel N; Keinan, Alon; Hao, Li; Atzmon, Gil; Burns, Edward; Ostrer, Harry; Price, Alkes L; Reich, David

    2011-04-01

    Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%-3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%-15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%-5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas.

  5. Genome-wide analysis of admixture and adaptation in the Africanized honeybee.

    PubMed

    Nelson, Ronald M; Wallberg, Andreas; Simões, Zilá Luz Paulino; Lawson, Daniel J; Webster, Matthew T

    2017-04-05

    Genetic exchange by hybridization or admixture can make an important contribution to evolution, and introgression of favourable alleles can facilitate adaptation to new environments. A small number of honeybees (Apis mellifera) with African ancestry were introduced to Brazil ~60 years ago, which dispersed and hybridized with existing managed populations of European origin, quickly spreading across much of the Americas in an example of a massive biological invasion. Here we analyse whole genome sequences of 32 Africanized honeybees sampled from throughout Brazil in order to study the effect of this process on genome diversity. By comparison with ancestral populations from Europe and Africa, we infer that these samples have 84% African ancestry, with the remainder from western European populations. However, this proportion varies across the genome and we identify signals of positive selection in regions with high European ancestry proportions. These observations are largely driven by one large gene-rich 1.4-Mbp segment on chromosome 11 where European haplotypes are present at a significantly elevated frequency and likely confer an adaptive advantage in the Africanized honeybee population. This region has previously been implicated in reproductive traits and foraging behaviour in worker bees. Finally, by analysing the distribution of ancestry tract lengths in the context of the known time of the admixture event, we are able to infer an average generation time of 2.0 years. Our analysis highlights the processes by which populations of mixed genetic ancestry form and adapt to new environments. This article is protected by copyright. All rights reserved.

  6. Genetic ancestry and indigenous heritage in a Native American descendant community in Bermuda.

    PubMed

    Gaieski, Jill B; Owings, Amanda C; Vilar, Miguel G; Dulik, Matthew C; Gaieski, David F; Gittelman, Rachel M; Lindo, John; Gau, Lydia; Schurr, Theodore G

    2011-11-01

    Discovered in the early 16th century by European colonists, Bermuda is an isolated set of islands located in the mid-Atlantic. Shortly after its discovery, Bermuda became the first English colony to forcibly import its labor by trafficking in enslaved Africans, white ethnic minorities, and indigenous Americans. Oral traditions circulating today among contemporary tribes from the northeastern United States recount these same events, while, in Bermuda, St. David's Islanders consider their histories to be linked to a complex Native American, European, and African past. To investigate the influence of historical events on biological ancestry and native cultural identity, we analyzed genetic variation in 111 members of Bermuda's self-proclaimed St. David's Island Native Community. Our results reveal that the majority of mitochondrial DNA (mtDNA) and Y-chromosome haplotypes are of African and West Eurasian origin. However, unlike other English-speaking New World colonies, most African mtDNA haplotypes appear to derive from central and southeast Africa, reflecting the extent of maritime activities in the region. In light of genealogical and oral historical data from the St. David's community, the low frequency of Native American mtDNA and NRY lineages may reflect the influence of genetic drift, the demographic impact of European colonization, and historical admixture with persons of non-native backgrounds, which began with the settlement of the islands. By comparing the genetic data with genealogical and historical information, we are able to reconstruct the complex history of this Bermudian community, which is unique among New World populations.

  7. Counting the founders: the matrilineal genetic ancestry of the Jewish Diaspora.

    PubMed

    Behar, Doron M; Metspalu, Ene; Kivisild, Toomas; Rosset, Saharon; Tzur, Shay; Hadid, Yarin; Yudkovsky, Guennady; Rosengarten, Dror; Pereira, Luisa; Amorim, Antonio; Kutuev, Ildus; Gurwitz, David; Bonne-Tamir, Batsheva; Villems, Richard; Skorecki, Karl

    2008-04-30

    The history of the Jewish Diaspora dates back to the Assyrian and Babylonian conquests in the Levant, followed by complex demographic and migratory trajectories over the ensuing millennia which pose a serious challenge to unraveling population genetic patterns. Here we ask whether phylogenetic analysis, based on highly resolved mitochondrial DNA (mtDNA) phylogenies can discern among maternal ancestries of the Diaspora. Accordingly, 1,142 samples from 14 different non-Ashkenazi Jewish communities were analyzed. A list of complete mtDNA sequences was established for all variants present at high frequency in the communities studied, along with high-resolution genotyping of all samples. Unlike the previously reported pattern observed among Ashkenazi Jews, the numerically major portion of the non-Ashkenazi Jews, currently estimated at 5 million people and comprised of the Moroccan, Iraqi, Iranian and Iberian Exile Jewish communities showed no evidence for a narrow founder effect, which did however characterize the smaller and more remote Belmonte, Indian and the two Caucasus communities. The Indian and Ethiopian Jewish sample sets suggested local female introgression, while mtDNAs in all other communities studied belong to a well-characterized West Eurasian pool of maternal lineages. Absence of sub-Saharan African mtDNA lineages among the North African Jewish communities suggests negligible or low level of admixture with females of the host populations among whom the African haplogroup (Hg) L0-L3 sub-clades variants are common. In contrast, the North African and Iberian Exile Jewish communities show influence of putative Iberian admixture as documented by mtDNA Hg HV0 variants. These findings highlight striking differences in the demographic history of the widespread Jewish Diaspora.

  8. How many rumbles are there? Acoustic variation and individual identity in the rumble vocalizations of African elephants (Loxodonta africana)

    NASA Astrophysics Data System (ADS)

    Soltis, Joseph M.; Savage, Anne; Leong, Kirsten M.

    2004-05-01

    The most commonly occurring elephant vocalization is the rumble, a frequency-modulated call with infrasonic components. Upwards of ten distinct rumble subtypes have been proposed, but little quantitative work on the acoustic properties of rumbles has been conducted. Rumble vocalizations (N=269) from six females housed at Disney's Animal Kingdom were analyzed. Vocalizations were recorded from microphones in collars around subject necks, and rumbles were digitized and measured using SIGNAL software. Sixteen acoustic variables were measured for each call, extracting both source and filter features. Multidimensional scaling analysis indicates that there are no acoustically distinct rumble subtypes, but that there is quantitative variation across rumbles. Discriminant function analysis showed that the acoustic characteristics of rumbles differ across females. A classification success rate of 65% was achieved when assigning unselected rumbles to one of the six females (test set =64 calls) according to the functions derived from the originally selected calls (training set =205 calls). The rumble is best viewed as a single call type with graded variation, but information regarding individual identity is encoded in female rumbles.

  9. Simulating carbon stocks and fluxes of an African tropical montane forest with an individual-based forest model.

    PubMed

    Fischer, Rico; Ensslin, Andreas; Rutten, Gemma; Fischer, Markus; Schellenberger Costa, David; Kleyer, Michael; Hemp, Andreas; Paulick, Sebastian; Huth, Andreas

    2015-01-01

    Tropical forests are carbon-dense and highly productive ecosystems. Consequently, they play an important role in the global carbon cycle. In the present study we used an individual-based forest model (FORMIND) to analyze the carbon balances of a tropical forest. The main processes of this model are tree growth, mortality, regeneration, and competition. Model parameters were calibrated using forest inventory data from a tropical forest at Mt. Kilimanjaro. The simulation results showed that the model successfully reproduces important characteristics of tropical forests (aboveground biomass, stem size distribution and leaf area index). The estimated aboveground biomass (385 t/ha) is comparable to biomass values in the Amazon and other tropical forests in Africa. The simulated forest reveals a gross primary production of 24 tcha(-1) yr(-1). Modeling above- and belowground carbon stocks, we analyzed the carbon balance of the investigated tropical forest. The simulated carbon balance of this old-growth forest is zero on average. This study provides an example of how forest models can be used in combination with forest inventory data to investigate forest structure and local carbon balances.

  10. Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

    PubMed Central

    Chen, Brian H.; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J.; Yanek, Lisa R.; Nalls, Michael A.; Comeau, Mary E.; Rasmussen-Torvik, Laura J.; Jensen, Richard A.; Evans, Daniel S.; Sun, Yan V.; An, Ping; Patel, Sanjay R.; Lu, Yingchang; Long, Jirong; Armstrong, Loren L.; Wagenknecht, Lynne; Yang, Lingyao; Snively, Beverly M.; Palmer, Nicholette D.; Mudgal, Poorva; Langefeld, Carl D.; Keene, Keith L.; Freedman, Barry I.; Mychaleckyj, Josyf C.; Nayak, Uma; Raffel, Leslie J.; Goodarzi, Mark O.; Chen, Y-D Ida; Taylor, Herman A.; Correa, Adolfo; Sims, Mario; Couper, David; Pankow, James S.; Boerwinkle, Eric; Adeyemo, Adebowale; Doumatey, Ayo; Chen, Guanjie; Mathias, Rasika A.; Vaidya, Dhananjay; Singleton, Andrew B.; Zonderman, Alan B.; Igo, Robert P.; Sedor, John R.; Kabagambe, Edmond K.; Siscovick, David S.; McKnight, Barbara; Rice, Kenneth; Liu, Yongmei; Hsueh, Wen-Chi; Zhao, Wei; Bielak, Lawrence F.; Kraja, Aldi; Province, Michael A.; Bottinger, Erwin P.; Gottesman, Omri; Cai, Qiuyin; Zheng, Wei; Blot, William J.; Lowe, William L.; Pacheco, Jennifer A.; Crawford, Dana C.; Grundberg, Elin; Rich, Stephen S.; Hayes, M. Geoffrey; Shu, Xiao-Ou; Loos, Ruth J. F.; Borecki, Ingrid B.; Peyser, Patricia A.; Cummings, Steven R.; Psaty, Bruce M.; Fornage, Myriam; Iyengar, Sudha K.; Evans, Michele K.; Becker, Diane M.; Kao, W. H. Linda; Wilson, James G.; Rotter, Jerome I.; Sale, Michèle M.; Liu, Simin; Rotimi, Charles N.; Bowden, Donald W.

    2014-01-01

    Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies. PMID:25102180

  11. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

    PubMed

    Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J; Yanek, Lisa R; Nalls, Michael A; Comeau, Mary E; Rasmussen-Torvik, Laura J; Jensen, Richard A; Evans, Daniel S; Sun, Yan V; An, Ping; Patel, Sanjay R; Lu, Yingchang; Long, Jirong; Armstrong, Loren L; Wagenknecht, Lynne; Yang, Lingyao; Snively, Beverly M; Palmer, Nicholette D; Mudgal, Poorva; Langefeld, Carl D; Keene, Keith L; Freedman, Barry I; Mychaleckyj, Josyf C; Nayak, Uma; Raffel, Leslie J; Goodarzi, Mark O; Chen, Y-D Ida; Taylor, Herman A; Correa, Adolfo; Sims, Mario; Couper, David; Pankow, James S; Boerwinkle, Eric; Adeyemo, Adebowale; Doumatey, Ayo; Chen, Guanjie; Mathias, Rasika A; Vaidya, Dhananjay; Singleton, Andrew B; Zonderman, Alan B; Igo, Robert P; Sedor, John R; Kabagambe, Edmond K; Siscovick, David S; McKnight, Barbara; Rice, Kenneth; Liu, Yongmei; Hsueh, Wen-Chi; Zhao, Wei; Bielak, Lawrence F; Kraja, Aldi; Province, Michael A; Bottinger, Erwin P; Gottesman, Omri; Cai, Qiuyin; Zheng, Wei; Blot, William J; Lowe, William L; Pacheco, Jennifer A; Crawford, Dana C; Grundberg, Elin; Rich, Stephen S; Hayes, M Geoffrey; Shu, Xiao-Ou; Loos, Ruth J F; Borecki, Ingrid B; Peyser, Patricia A; Cummings, Steven R; Psaty, Bruce M; Fornage, Myriam; Iyengar, Sudha K; Evans, Michele K; Becker, Diane M; Kao, W H Linda; Wilson, James G; Rotter, Jerome I; Sale, Michèle M; Liu, Simin; Rotimi, Charles N; Bowden, Donald W

    2014-08-01

    Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.

  12. The Meaning of Adversity within Traditional K-12 Math Classrooms in the United States from the Perspective of African-American Individuals

    ERIC Educational Resources Information Center

    Muldrew, Lola Melissa

    2012-01-01

    An important consequence of a deeply rooted, mono-cultural rubric for acceptable school participation in the United States has been that African-American students in traditional K-12 math classrooms tend to be labeled as academically "at risk." This qualitative investigation responds to said categorization by examining African-American…

  13. Multiple Case Studies of Literacy Practices Utilized by Intermediate Grade Teachers Which Enable African American Males to Become Literate Individuals--What's Going On?

    ERIC Educational Resources Information Center

    Wooten, Cynthia Brooks

    2010-01-01

    The purpose of this qualitative study was to investigate ways in which six teachers in the intermediate grades at one urban and one rural school enabled their African American male students to be successful in their literacy efforts. It was my assumption that successful teachers of African American males would also be teachers who integrated…

  14. A diffusion tensor imaging and neuropsychological study of prospective memory impairment in South African HIV positive individuals.

    PubMed

    Hoare, Jacqueline; Jacqueline, Hoare; Westgarth-Taylor, Jenny; Jenny, Westgarth-Taylor; Fouche, Jean-Paul; Jean-Paul, Fouche; Spottiswoode, Bruce; Bruce, Spottiswoode; Paul, Robert; Robert, Paul; Thomas, Kevin; Kevin, Thomas; Stein, Dan; Dan, Stein; Joska, John; John, Joska

    2012-09-01

    HIV-associated prospective memory (ProM) impairment has emerged, in earlier studies as a significant predictor of medication management and independence in activities of daily living. The relationship between ProM and white matter integrity in HIV has not previously been investigated. Participants, including 128 HIV-infected individuals and 32 healthy controls, were assessed using a comprehensive neuropsychological evaluation and both objective and subjective measures of ProM. Diffusion tensor imaging (DTI) was utilized to investigate the relationship of white matter integrity to ProM in a randomly selected subsample of 40 HIV positive subjects, using a whole brain voxel-based approach to define fractional anisotrophy (FA) and mean diffusion (MD). Total prospective memory was significantly poorer in the HIV positive group when compared with healthy controls (p = 0.023). Time-based ProM was poorer in the HIV group compared to healthy controls both without prompts (p = 0.001) and with prompts (p = 0.001). Poor Total ProM score correlated with performance on neuropsychological tests of executive functioning, information processing speed, learning, and working memory (p < 0.05). Those HIV positive participants with poor ProM had significantly decreased FA in the regions of superior corona radiata (p = 0.0035), the corpus collosum (p = 0.006) and the cingulum (p = 0.0033) when compared to those who were HIV positive with good ProM. This study reinforces the importance of ProM assessment in HIV.

  15. In search of genetic markers for nonsyndromic deafness in Africa: a study in Cameroonians and Black South Africans with the GJB6 and GJA1 candidate genes.

    PubMed

    Bosch, Jason; Lebeko, Kamogelo; Nziale, Jean Jacques Noubiap; Dandara, Collet; Makubalo, Nomlindo; Wonkam, Ambroise

    2014-07-01

    Deafness is the most common sensory disability in the world and has a variety of causes. Globally, mutations in GJB2 have been shown to play a major role in nonsyndromic deafness, but this has not been seen in Africans. Two other connexin genes, GJB6 and GJA1, have been implicated in hearing loss but have seldom been investigated in African populations. We set out to investigate the role of genetic variation in GJB6 and GJA1 in a group of Cameroonian and South African Blacks with nonsyndromic recessive hearing loss. A subset of 100 patients, affected with nonsyndromic hearing loss, from a cohort that was previously shown not to have GJB2 mutation, was analyzed by Sanger sequencing of the entire coding regions of GJB6 and GJA1. In addition, the large-scale GJB6-D3S1830 deletion was also investigated. No pathogenic mutation was detected in either GJB6 or GJA1, nor was the GJB6-D3S1830 deletion detected. There were no statistically significant differences in sequence variants between patients and controls. Mutations in GJB6 and GJA1 are not a major cause of nonsyndromic deafness in this group of Africans from Cameroon and South Africa. Currently, there is no sufficient evidence to support their testing in a clinical setting for individuals of African ancestry.

  16. Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.

    PubMed

    Cai, Qiuyin; Wen, Wanqing; Qu, Shimian; Li, Guoliang; Egan, Kathleen M; Chen, Kexin; Deming, Sandra L; Shen, Hongbing; Shen, Chen-Yang; Gammon, Marilie D; Blot, William J; Matsuo, Keitaro; Haiman, Christopher A; Khoo, Ui Soon; Iwasaki, Motoki; Santella, Regina M; Zhang, Lina; Fair, Alecia Malin; Hu, Zhibin; Wu, Pei-Ei; Signorello, Lisa B; Titus-Ernstoff, Linda; Tajima, Kazuo; Henderson, Brian E; Chan, Kelvin Y K; Kasuga, Yoshio; Newcomb, Polly A; Zheng, Hong; Cui, Yong; Wang, Furu; Shieh, Ya-Lan; Iwata, Hiroji; Le Marchand, Loic; Chan, Sum Yin; Shrubsole, Martha J; Trentham-Dietz, Amy; Tsugane, Shoichiro; Garcia-Closas, Montserrat; Long, Jirong; Li, Chun; Shi, Jiajun; Huang, Bo; Xiang, Yong-Bing; Gao, Yu-Tang; Lu, Wei; Shu, Xiao-Ou; Zheng, Wei

    2011-02-15

    We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10⁻³⁰], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10⁻⁴], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r² = 0.83) populations, but not in Africans (r² = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region.

  17. Assessing Patterns of Admixture and Ancestry in Canadian Honey Bees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Canada has a large beekeeping industry comprised of 8483 beekeepers managing 672094 23 colonies. Canadian honey bees, like all honey bees in the New World, originate from centuries of importation of predominately European honey bees, but their precise ancestry remains unknown. There have been no i...

  18. Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm.

    PubMed

    Hoffmann, Thomas J; Zhan, Yiping; Kvale, Mark N; Hesselson, Stephanie E; Gollub, Jeremy; Iribarren, Carlos; Lu, Yontao; Mei, Gangwu; Purdy, Matthew M; Quesenberry, Charles; Rowell, Sarah; Shapero, Michael H; Smethurst, David; Somkin, Carol P; Van den Eeden, Stephen K; Walter, Larry; Webster, Teresa; Whitmer, Rachel A; Finn, Andrea; Schaefer, Catherine; Kwok, Pui-Yan; Risch, Neil

    2011-12-01

    Four custom Axiom genotyping arrays were designed for a genome-wide association (GWA) study of 100,000 participants from the Kaiser Permanente Research Program on Genes, Environment and Health. The array optimized for individuals of European race/ethnicity was previously described. Here we detail the development of three additional microarrays optimized for individuals of East Asian, African American, and Latino race/ethnicity. For these arrays, we decreased redundancy of high-performing SNPs to increase SNP capacity. The East Asian array was designed using greedy pairwise SNP selection. However, removing SNPs from the target set based on imputation coverage is more efficient than pairwise tagging. Therefore, we developed a novel hybrid SNP selection method for the African American and Latino arrays utilizing rounds of greedy pairwise SNP selection, followed by removal from the target set of SNPs covered by imputation. The arrays provide excellent genome-wide coverage and are valuable additions for large-scale GWA studies.

  19. Inference of biogeographical ancestry across central regions of Eurasia.

    PubMed

    Bulbul, O; Filoglu, G; Zorlu, T; Altuncul, H; Freire-Aradas, A; Söchtig, J; Ruiz, Y; Klintschar, M; Triki-Fendri, S; Rebai, A; Phillips, C; Lareu, M V; Carracedo, Á; Schneider, P M

    2016-01-01

    The inference of biogeographical ancestry (BGA) can provide useful information for forensic investigators when there are no suspects to be compared with DNA collected at the crime scene or when no DNA database matches exist. Although public databases are increasing in size and population scope, there is a lack of information regarding genetic variation in Eurasian populations, especially in central regions such as the Middle East. Inhabitants of these regions show a high degree of genetic admixture, characterized by an allele frequency cline running from NW Europe to East Asia. Although a proper differentiation has been established between the cline extremes of western Europe and South Asia, populations geographically located in between, i.e, Middle East and Mediterranean populations, require more detailed study in order to characterize their genetic background as well as to further understand their demographic histories. To initiate these studies, three ancestry informative SNP (AI-SNP) multiplex panels: the SNPforID 34-plex, Eurasiaplex and a novel 33-plex assay were used to describe the ancestry patterns of a total of 24 populations ranging across the longitudinal axis from NW Europe to East Asia. Different ancestry inference approaches, including STRUCTURE, PCA, DAPC and Snipper Bayes analysis, were applied to determine relationships among populations. The structure results show differentiation between continental groups and a NW to SE allele frequency cline running across Eurasian populations. This study adds useful population data that could be used as reference genotypes for future ancestry investigations in forensic cases. The 33-plex assay also includes pigmentation predictive SNPs, but this study primarily focused on Eurasian population differentiation using 33-plex and its combination with the other two AI-SNP sets.

  20. Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry

    PubMed Central

    Paula, André E.; Pereira, Rui; Andrade, Carlos E.; Felicio, Paula S.; Souza, Cristiano P.; Mendes, Deise R.P.; Volc, Sahlua; Berardinelli, Gustavo N.; Grasel, Rebeca S.; Sabato, Cristina S.; Viana, Danilo V.; Machado, José Carlos; Costa, José Luis; Mauad, Edmundo C.; Scapulatempo-Neto, Cristovam; Arun, Banu; Reis, Rui M.; Palmero, Edenir I.

    2016-01-01

    Background There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA. Results Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian. Materials and methods This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry. Conclusions This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families. PMID:27741520

  1. [Physical growth in stature of school children of Japanese ancestry in the city of São Paulo, Brazil

    PubMed

    Kac; Santos

    1996-04-01

    This paper reports the results of a cross-sectional survey describing the growth in stature of a sample of school children of Japanese ancestry (three or four grandparents born in Japan) and of high socio-economic status living in São Paulo, Brazil. The sample comprises 124 individuals 7-10 years of age, of both sexes. The results show that the children present mean values of stature below the median values of the NCHS curves ("National Center for Health Statistics", U.S.A.). The values are similar to the medians of a sample of Japanese children and below those of well-to-do Brazilian children of non-Japanese ancestry studied by the PNSN ("Pesquisa Nacional sobre Saúde e Nutrição", Brazil). The findings do not support the hypothesis of uniformity of growth potential in stature, casting doubts on the utilization of a single anthropometric reference in the assessment of nutritional status.

  2. Detecting structure of haplotypes and local ancestry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present a two-layer hidden Markov model to detect the structure of haplotypes for unrelated individuals. This allows us to model two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local an...

  3. Developmental validation of mitochondrial DNA genotyping assays for adept matrilineal inference of biogeographic ancestry at a continental level.

    PubMed

    Chaitanya, Lakshmi; van Oven, Mannis; Weiler, Natalie; Harteveld, Joyce; Wirken, Laura; Sijen, Titia; de Knijff, Peter; Kayser, Manfred

    2014-07-01

    Mitochondrial DNA (mtDNA) can be used for matrilineal biogeographic ancestry prediction and can thus provide investigative leads towards identifying unknown suspects, when conventional autosomal short tandem repeat (STR) profiling fails to provide a match. Recently, six multiplex genotyping assays targeting 62 ancestry-informative mitochondrial single nucleotide polymorphisms (mt-SNPs) were developed. This hierarchical system of assays allows detection of the major haplogroups present in Africa, America, Western Eurasia, Eastern Eurasia, Australia and Oceania, thus revealing the broad geographic region of matrilineal origin of a DNA donor. Here, we provide a forensic developmental validation study of five multiplex assays targeting all the 62 ancestry-informative mt-SNPs following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. We demonstrate that the assays are highly sensitive; being able to produce full profiles at input DNA amounts of as little as 1pg. The assays were shown to be highly robust and efficient in providing information from degraded samples and from simulated casework samples of different substrates such as blood, semen, hair, saliva and trace DNA samples. Reproducible results were successfully achieved from concordance testing across three independent laboratories depicting the ease and reliability of these assays. Overall, our results demonstrate the suitability of these five mt-SNP assays for application to forensic casework and other purposes aiming to establish an individual's matrilineal genetic ancestry. With this validated tool, it is now possible to determine the matrilineal biogeographic origin of unknown individuals on the level of continental resolution from forensic DNA samples to provide investigative leads in criminal and missing person cases where autosomal STR profiling is uninformative.

  4. Ancestry and demography and descendants of Iron Age nomads of the Eurasian Steppe

    PubMed Central

    Unterländer, Martina; Palstra, Friso; Lazaridis, Iosif; Pilipenko, Aleksandr; Hofmanová, Zuzana; Groß, Melanie; Sell, Christian; Blöcher, Jens; Kirsanow, Karola; Rohland, Nadin; Rieger, Benjamin; Kaiser, Elke; Schier, Wolfram; Pozdniakov, Dimitri; Khokhlov, Aleksandr; Georges, Myriam; Wilde, Sandra; Powell, Adam; Heyer, Evelyne; Currat, Mathias; Reich, David; Samashev, Zainolla; Parzinger, Hermann; Molodin, Vyacheslav I.; Burger, Joachim

    2017-01-01

    During the 1st millennium before the Common Era (BCE), nomadic tribes associated with the Iron Age Scythian culture spread over the Eurasian Steppe, covering a territory of more than 3,500 km in breadth. To understand the demographic processes behind the spread of the Scythian culture, we analysed genomic data from eight individuals and a mitochondrial dataset of 96 individuals originating in eastern and western parts of the Eurasian Steppe. Genomic inference reveals that Scythians in the east and the west of the steppe zone can best be described as a mixture of Yamnaya-related ancestry and an East Asian component. Demographic modelling suggests independent origins for eastern and western groups with ongoing gene-flow between them, plausibly explaining the striking uniformity of their material culture. We also find evidence that significant gene-flow from east to west Eurasia must have occurred early during the Iron Age. PMID:28256537

  5. Hereditary motor and sensory neuropathy (proximal dominant form, HMSN-P) among Brazilians of Japanese ancestry.

    PubMed

    Maeda, Kengo; Sugiura, Makoto; Kato, Hiroko; Sanada, Mitsuru; Kawai, Hiromichi; Yasuda, Hitoshi

    2007-11-01

    Hereditary motor and sensory neuropathy (proximal dominant form, HMSN-P) has been reported exclusively from Okinawa Prefecture in Japan. We herein report three brothers with HMSN-P who are among Brazilians of Japanese ancestry. They showed the typical clinical manifestations and were compatible with HMSN-P. Okinawa Prefecture has been a site of emigration to other countries, mainly in South America, since 1908. Although this is the first reported familial case of HMSN-P occurring outside Japan, it is estimated that there are 19 or 20 individuals with HMSN-P among these emigrants. Since HMSN-P might be misdiagnosed as familial amyotrophic lateral sclerosis or spinal muscular atrophy, neurologists in countries where individuals of Okinawan extraction reside should be aware of this hereditary neuropathy. HMSN-P should no longer be regarded as an endemic condition limited to Okinawa.

  6. Ancestry and demography and descendants of Iron Age nomads of the Eurasian Steppe

    NASA Astrophysics Data System (ADS)

    Unterländer, Martina; Palstra, Friso; Lazaridis, Iosif; Pilipenko, Aleksandr; Hofmanová, Zuzana; Groß, Melanie; Sell, Christian; Blöcher, Jens; Kirsanow, Karola; Rohland, Nadin; Rieger, Benjamin; Kaiser, Elke; Schier, Wolfram; Pozdniakov, Dimitri; Khokhlov, Aleksandr; Georges, Myriam; Wilde, Sandra; Powell, Adam; Heyer, Evelyne; Currat, Mathias; Reich, David; Samashev, Zainolla; Parzinger, Hermann; Molodin, Vyacheslav I.; Burger, Joachim

    2017-03-01

    During the 1st millennium before the Common Era (BCE), nomadic tribes associated with the Iron Age Scythian culture spread over the Eurasian Steppe, covering a territory of more than 3,500 km in breadth. To understand the demographic processes behind the spread of the Scythian culture, we analysed genomic data from eight individuals and a mitochondrial dataset of 96 individuals originating in eastern and western parts of the Eurasian Steppe. Genomic inference reveals that Scythians in the east and the west of the steppe zone can best be described as a mixture of Yamnaya-related ancestry and an East Asian component. Demographic modelling suggests independent origins for eastern and western groups with ongoing gene-flow between them, plausibly explaining the striking uniformity of their material culture. We also find evidence that significant gene-flow from east to west Eurasia must have occurred early during the Iron Age.

  7. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.

    PubMed

    Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I; Conti, David V; Schumacher, Fredrick; Han, Ying; Benlloch, Sara; Hazelett, Dennis J; Wang, Zhaoming; Saunders, Ed; Leongamornlert, Daniel; Lindstrom, Sara; Jugurnauth-Little, Sara; Dadaev, Tokhir; Tymrakiewicz, Malgorzata; Stram, Daniel O; Rand, Kristin; Wan, Peggy; Stram, Alex; Sheng, Xin; Pooler, Loreall C; Park, Karen; Xia, Lucy; Tyrer, Jonathan; Kolonel, Laurence N; Le Marchand, Loic; Hoover, Robert N; Machiela, Mitchell J; Yeager, Merideth; Burdette, Laurie; Chung, Charles C; Hutchinson, Amy; Yu, Kai; Goh, Chee; Ahmed, Mahbubl; Govindasami, Koveela; Guy, Michelle; Tammela, Teuvo L J; Auvinen, Anssi; Wahlfors, Tiina; Schleutker, Johanna; Visakorpi, Tapio; Leinonen, Katri A; Xu, Jianfeng; Aly, Markus; Donovan, Jenny; Travis, Ruth C; Key, Tim J; Siddiq, Afshan; Canzian, Federico; Khaw, Kay-Tee; Takahashi, Atsushi; Kubo, Michiaki; Pharoah, Paul; Pashayan, Nora; Weischer, Maren; Nordestgaard, Borge G; Nielsen, Sune F; Klarskov, Peter; Røder, Martin Andreas; Iversen, Peter; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Stanford, Janet L; Kolb, Suzanne; Holt, Sarah; Knudsen, Beatrice; Coll, Antonio Hurtado; Gapstur, Susan M; Diver, W Ryan; Stevens, Victoria L; Maier, Christiane; Luedeke, Manuel; Herkommer, Kathleen; Rinckleb, Antje E; Strom, Sara S; Pettaway, Curtis; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; Cannon-Albright, Lisa; Cybulski, Cezary; Wokołorczyk, Dominika; Kluźniak, Wojciech; Park, Jong; Sellers, Thomas; Lin, Hui-Yi; Isaacs, William B; Partin, Alan W; Brenner, Hermann; Dieffenbach, Aida Karina; Stegmaier, Christa; Chen, Constance; Giovannucci, Edward L; Ma, Jing; Stampfer, Meir; Penney, Kathryn L; Mucci, Lorelei; John, Esther M; Ingles, Sue A; Kittles, Rick A; Murphy, Adam B; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej M; Blot, William; Signorello, Lisa B; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, Cristina; Wu, Suh-Yuh; Hennis, Anselm; Kibel, Adam S; Rybicki, Benjamin A; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Batra, Jyotsna; Clements, Judith; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Witte, John S; Casey, Graham; Gillanders, Elizabeth M; Seminara, Daniella; Riboli, Elio; Hamdy, Freddie C; Coetzee, Gerhard A; Li, Qiyuan; Freedman, Matthew L; Hunter, David J; Muir, Kenneth; Gronberg, Henrik; Neal, David E; Southey, Melissa; Giles, Graham G; Severi, Gianluca; Cook, Michael B; Nakagawa, Hidewaki; Wiklund, Fredrik; Kraft, Peter; Chanock, Stephen J; Henderson, Brian E; Easton, Douglas F; Eeles, Rosalind A; Haiman, Christopher A

    2014-10-01

    Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

  8. The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry.

    PubMed

    Waldman, Yedael Y; Biddanda, Arjun; Davidson, Natalie R; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

    2016-01-01

    The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19-33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so.

  9. The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry

    PubMed Central

    Davidson, Natalie R.; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L.; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

    2016-01-01

    The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19–33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so. PMID:27010569

  10. Meta-analysis of loci associated with age at natural menopause in African-American women

    PubMed Central

    Chen, Christina T.L.; Liu, Ching-Ti; Chen, Gary K.; Andrews, Jeanette S.; Arnold, Alice M.; Dreyfus, Jill; Franceschini, Nora; Garcia, Melissa E.; Kerr, Kathleen F.; Li, Guo; Lohman, Kurt K.; Musani, Solomon K.; Nalls, Michael A.; Raffel, Leslie J.; Smith, Jennifer; Ambrosone, Christine B.; Bandera, Elisa V.; Bernstein, Leslie; Britton, Angela; Brzyski, Robert G.; Cappola, Anne; Carlson, Christopher S.; Couper, David; Deming, Sandra L.; Goodarzi, Mark O.; Heiss, Gerardo; John, Esther M.; Lu, Xiaoning; Le Marchand, Loic; Marciante, Kristin; Mcknight, Barbara; Millikan, Robert; Nock, Nora L.; Olshan, Andrew F.; Press, Michael F.; Vaiyda, Dhananjay; Woods, Nancy F.; Taylor, Herman A.; Zhao, Wei; Zheng, Wei; Evans, Michele K.; Harris, Tamara B.; Henderson, Brian E.; Kardia, Sharon L.R.; Kooperberg, Charles; Liu, Yongmei; Mosley, Thomas H.; Psaty, Bruce; Wellons, Melissa; Windham, Beverly G.; Zonderman, Alan B.; Cupples, L. Adrienne; Demerath, Ellen W.; Haiman, Christopher; Murabito, Joanne M.; Rajkovic, Aleksandar

    2014-01-01

    Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA. PMID:24493794

  11. Meta-analysis of loci associated with age at natural menopause in African-American women.

    PubMed

    Chen, Christina T L; Liu, Ching-Ti; Chen, Gary K; Andrews, Jeanette S; Arnold, Alice M; Dreyfus, Jill; Franceschini, Nora; Garcia, Melissa E; Kerr, Kathleen F; Li, Guo; Lohman, Kurt K; Musani, Solomon K; Nalls, Michael A; Raffel, Leslie J; Smith, Jennifer; Ambrosone, Christine B; Bandera, Elisa V; Bernstein, Leslie; Britton, Angela; Brzyski, Robert G; Cappola, Anne; Carlson, Christopher S; Couper, David; Deming, Sandra L; Goodarzi, Mark O; Heiss, Gerardo; John, Esther M; Lu, Xiaoning; Le Marchand, Loic; Marciante, Kristin; Mcknight, Barbara; Millikan, Robert; Nock, Nora L; Olshan, Andrew F; Press, Michael F; Vaiyda, Dhananjay; Woods, Nancy F; Taylor, Herman A; Zhao, Wei; Zheng, Wei; Evans, Michele K; Harris, Tamara B; Henderson, Brian E; Kardia, Sharon L R; Kooperberg, Charles; Liu, Yongmei; Mosley, Thomas H; Psaty, Bruce; Wellons, Melissa; Windham, Beverly G; Zonderman, Alan B; Cupples, L Adrienne; Demerath, Ellen W; Haiman, Christopher; Murabito, Joanne M; Rajkovic, Aleksandar

    2014-06-15

    Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.

  12. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

    PubMed

    Wen, Wanqing; Zheng, Wei; Okada, Yukinori; Takeuchi, Fumihiko; Tabara, Yasuharu; Hwang, Joo-Yeon; Dorajoo, Rajkumar; Li, Huaixing; Tsai, Fuu-Jen; Yang, Xiaobo; He, Jiang; Wu, Ying; He, Meian; Zhang, Yi; Liang, Jun; Guo, Xiuqing; Sheu, Wayne Huey-Herng; Delahanty, Ryan; Guo, Xingyi; Kubo, Michiaki; Yamamoto, Ken; Ohkubo, Takayoshi; Go, Min Jin; Liu, Jian Jun; Gan, Wei; Chen, Ching-Chu; Gao, Yong; Li, Shengxu; Lee, Nanette R; Wu, Chen; Zhou, Xueya; Song, Huaidong; Yao, Jie; Lee, I-Te; Long, Jirong; Tsunoda, Tatsuhiko; Akiyama, Koichi; Takashima, Naoyuki; Cho, Yoon Shin; Ong, Rick Th; Lu, Ling; Chen, Chien-Hsiun; Tan, Aihua; Rice, Treva K; Adair, Linda S; Gui, Lixuan; Allison, Matthew; Lee, Wen-Jane; Cai, Qiuyin; Isomura, Minoru; Umemura, Satoshi; Kim, Young Jin; Seielstad, Mark; Hixson, James; Xiang, Yong-Bing; Isono, Masato; Kim, Bong-Jo; Sim, Xueling; Lu, Wei; Nabika, Toru; Lee, Juyoung; Lim, Wei-Yen; Gao, Yu-Tang; Takayanagi, Ryoichi; Kang, Dae-Hee; Wong, Tien Yin; Hsiung, Chao Agnes; Wu, I-Chien; Juang, Jyh-Ming Jimmy; Shi, Jiajun; Choi, Bo Youl; Aung, Tin; Hu, Frank; Kim, Mi Kyung; Lim, Wei Yen; Wang, Tzung-Dao; Shin, Min-Ho; Lee, Jeannette; Ji, Bu-Tian; Lee, Young-Hoon; Young, Terri L; Shin, Dong Hoon; Chun, Byung-Yeol; Cho, Myeong-Chan; Han, Bok-Ghee; Hwu, Chii-Min; Assimes, Themistocles L; Absher, Devin; Yan, Xiaofei; Kim, Eric; Kuo, Jane Z; Kwon, Soonil; Taylor, Kent D; Chen, Yii-Der I; Rotter, Jerome I; Qi, Lu; Zhu, Dingliang; Wu, Tangchun; Mohlke, Karen L; Gu, Dongfeng; Mo, Zengnan; Wu, Jer-Yuarn; Lin, Xu; Miki, Tetsuro; Tai, E Shyong; Lee, Jong-Young; Kato, Norihiro; Shu, Xiao-Ou; Tanaka, Toshihiro

    2014-10-15

    Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

  13. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

    PubMed Central

    Wen, Wanqing; Zheng, Wei; Okada, Yukinori; Takeuchi, Fumihiko; Tabara, Yasuharu; Hwang, Joo-Yeon; Dorajoo, Rajkumar; Li, Huaixing; Tsai, Fuu-Jen; Yang, Xiaobo; He, Jiang; Wu, Ying; He, Meian; Zhang, Yi; Liang, Jun; Guo, Xiuqing; Sheu, Wayne Huey-Herng; Delahanty, Ryan; Guo, Xingyi; Kubo, Michiaki; Yamamoto, Ken; Ohkubo, Takayoshi; Go, Min Jin; Liu, Jian Jun; Gan, Wei; Chen, Ching-Chu; Gao, Yong; Li, Shengxu; Lee, Nanette R.; Wu, Chen; Zhou, Xueya; Song, Huaidong; Yao, Jie; Lee, I-Te; Long, Jirong; Tsunoda, Tatsuhiko; Akiyama, Koichi; Takashima, Naoyuki; Cho, Yoon Shin; Ong, Rick TH; Lu, Ling; Chen, Chien-Hsiun; Tan, Aihua; Rice, Treva K; Adair, Linda S.; Gui, Lixuan; Allison, Matthew; Lee, Wen-Jane; Cai, Qiuyin; Isomura, Minoru; Umemura, Satoshi; Kim, Young Jin; Seielstad, Mark; Hixson, James; Xiang, Yong-Bing; Isono, Masato; Kim, Bong-Jo; Sim, Xueling; Lu, Wei; Nabika, Toru; Lee, Juyoung; Lim, Wei-Yen; Gao, Yu-Tang; Takayanagi, Ryoichi; Kang, Dae-Hee; Wong, Tien Yin; Hsiung, Chao Agnes; Wu, I-Chien; Juang, Jyh-Ming Jimmy; Shi, Jiajun; Choi, Bo Youl; Aung, Tin; Hu, Frank; Kim, Mi Kyung; Lim, Wei Yen; Wang, Tzung-Dao; Shin, Min-Ho; Lee, Jeannette; Ji, Bu-Tian; Lee, Young-Hoon; Young, Terri L.; Shin, Dong Hoon; Chun, Byung-Yeol; Cho, Myeong-Chan; Han, Bok-Ghee; Hwu, Chii-Min; Assimes, Themistocles L.; Absher, Devin; Yan, Xiaofei; Kim, Eric; Kuo, Jane Z.; Kwon, Soonil; Taylor, Kent D.; Chen, Yii-Der I.; Rotter, Jerome I.; Qi, Lu; Zhu, Dingliang; Wu, Tangchun; Mohlke, Karen L.; Gu, Dongfeng; Mo, Zengnan; Wu, Jer-Yuarn; Lin, Xu; Miki, Tetsuro; Tai, E. Shyong; Lee, Jong-Young; Kato, Norihiro; Shu, Xiao-Ou; Tanaka, Toshihiro

    2014-01-01

    Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity. PMID:24861553

  14. African American Leadership in Urban Institutions of Higher Education: A Case Narrative of the Social, Cultural, and Institutional Impact of an Individual Leader at a Historically White Institution

    ERIC Educational Resources Information Center

    Martin, Robin L.

    2013-01-01

    Leadership remains an important topic across various disciples. The continuous demonstration of effective leadership and its impact on institutions and society fuels the inquiry into the various ways, behaviors, traits, and situations in which leaders and leadership are successful (Kezar & Lester, 2011). As more African Americans advance in…

  15. Population Ancestry and Genetic Risk for Diabetes and Kidney, Cardiovascular, and Bone Disease: Modifiable Environmental Factors May Produce the Cures

    PubMed Central

    Freedman, Barry I.; Divers, Jasmin; Palmer, Nicholette D.

    2013-01-01

    Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This manuscript provides evidence in support of differential allele frequency distributions that underlie the higher rates of non-diabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biologic factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The current era of precision medicine will couple one’s genetic make-up with specific therapies to reduce rates of disease based on presence of disease-specific alleles. PMID:23896482

  16. Population ancestry and genetic risk for diabetes and kidney, cardiovascular, and bone disease: modifiable environmental factors may produce the cures.

    PubMed

    Freedman, Barry I; Divers, Jasmin; Palmer, Nicholette D

    2013-12-01

    Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This article provides evidence in support of differential allele frequency distributions that underlie the higher rates of nondiabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biological factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The present era of precision medicine will couple one's genetic makeup with specific therapies to reduce rates of disease based on the presence of disease-specific alleles.

  17. The Contribution of Biogeographic Ancestry and Socioeconomic Status to Racial/Ethnic Disparities in Type 2 Diabetes: Results from the Boston Area Community Health (BACH) Survey

    PubMed Central

    Piccolo, Rebecca S.; Pearce, Neil; Araujo, Andre B.; McKinlay, John B.

    2014-01-01

    Purpose Racial/ethnic disparities in the incidence of type 2 diabetes (T2DM) are well documented and many researchers have proposed that biogeographical ancestry (BGA) may play a role in these disparities. However, studies examining the role of BGA on T2DM have produced mixed results to date. Therefore, the objective of this research is to quantify the contribution of BGA to racial/ethnic disparities in T2DM incidence controlling for the mediating influences of socioeconomic factors. Methods We analyzed data from the Boston Area Community Health (BACH) Survey, a prospective cohort with approximately equal numbers of Black, Hispanic, and White participants. We used Ancestry Informative Markers to calculate the percentages of West African and Native American ancestry of participants. We used logistic regression with g-computation to analyze the contribution of BGA and socioeconomic factors to racial/ethnic disparities in T2DM incidence. Results We found that socioeconomic factors accounted for 44.7% of the total effect of T2DM attributed to Black race and 54.9% of the effect attributed to Hispanic ethnicity. We found that BGA had almost no direct association with T2DM and was almost entirely mediated by self-identified race/ethnicity and socioeconomic factors. Conclusions It is likely that non-genetic factors, specifically socioeconomic factors, account for much of the reported racial/ethnic disparities in T2DM incidence. PMID:25088753

  18. Mosaic maternal ancestry in the Great Lakes region of East Africa.

    PubMed

    Gomes, Verónica; Pala, Maria; Salas, Antonio; Álvarez-Iglesias, Vanesa; Amorim, António; Gómez-Carballa, Alberto; Carracedo, Ángel; Clarke, Douglas J; Hill, Catherine; Mormina, Maru; Shaw, Marie-Anne; Dunne, David W; Pereira, Rui; Pereira, Vânia; Prata, Maria João; Sánchez-Diz, Paula; Rito, Teresa; Soares, Pedro; Gusmão, Leonor; Richards, Martin B

    2015-09-01

    The Great Lakes lie within a region of East Africa with very high human genetic diversity, home of many ethno-linguistic groups usually assumed to be the product of a small number of major dispersals. However, our knowledge of these dispersals relies primarily on the inferences of historical, linguistics and oral traditions, with attempts to match up the archaeological evidence where possible. This is an obvious area to which archaeogenetics can contribute, yet Uganda, at the heart of these developments, has not been studied for mitochondrial DNA (mtDNA) variation. Here, we compare mtDNA lineages at this putative genetic crossroads across 409 representatives of the major language groups: Bantu speakers and Eastern and Western Nilotic speakers. We show that Uganda harbours one of the highest mtDNA diversities within and between linguistic groups, with the various groups significantly differentiated from each other. Despite an inferred linguistic origin in South Sudan, the data from the two Nilotic-speaking groups point to a much more complex history, involving not only possible dispersals from Sudan and the Horn but also large-scale assimilation of autochthonous lineages within East Africa and even Uganda itself. The Eastern Nilotic group also carries signals characteristic of West-Central Africa, primarily due to Bantu influence, whereas a much stronger signal in the Western Nilotic group suggests direct West-Central African ancestry. Bantu speakers share lineages with both Nilotic groups, and also harbour East African lineages not found in Western Nilotic speakers, likely due to assimilating indigenous populations since arriving in the region ~3000 years ago.

  19. Africanization of a feral honey bee (Apis mellifera) population in South Texas: does a decade make a difference?

    PubMed

    Rangel, Juliana; Giresi, Melissa; Pinto, Maria Alice; Baum, Kristen A; Rubink, William L; Coulson, Robert N; Johnston, John Spencer

    2016-04-01

    The arrival to the United States of the Africanized honey bee, a hybrid between European subspecies and the African subspecies Apis mellifera scutellata, is a remarkable model for the study of biological invasions. This immigration has created an opportunity to study the dynamics of secondary contact of honey bee subspecies from African and European lineages in a feral population in South Texas. An 11-year survey of this population (1991-2001) showed that mitochondrial haplotype frequencies changed drastically over time from a resident population of eastern and western European maternal ancestry, to a population dominated by the African haplotype. A subsequent study of the nuclear genome showed that the Africanization process included bidirectional gene flow between European and Africanized honey bees, giving rise to a new panmictic mixture of A. m. scutellata- and European-derived genes. In this study, we examined gene flow patterns in the same population 23 years after the first hybridization event occurred. We found 28 active colonies inhabiting 92 tree cavities surveyed in a 5.14 km(2) area, resulting in a colony density of 5.4 colonies/km(2). Of these 28 colonies, 25 were of A. m. scutellata maternal ancestry, and three were of western European maternal ancestry. No colonies of eastern European maternal ancestry were detected, although they were present in the earlier samples. Nuclear DNA revealed little change in the introgression of A. m. scutellata-derived genes into the population compared to previous surveys. Our results suggest this feral population remains an admixed swarm with continued low levels of European ancestry and a greater presence of African-derived mitochondrial genetic composition.

  20. Genome-wide association studies in Africans and African Americans: Expanding the Framework of the Genomics of Human Traits and Disease

    PubMed Central

    Peprah, Emmanuel; Xu, Huichun; Tekola-Ayele, Fasil; Royal, Charmaine D.

    2014-01-01

    Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance, and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago, and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent-African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions. PMID:25427668

  1. The Hmong Diaspora: preserved South-East Asian genetic ancestry in French Guianese Asians.

    PubMed

    Brucato, Nicolas; Mazières, Stéphane; Guitard, Evelyne; Giscard, Pierre-Henri; Bois, Etienne; Larrouy, Georges; Dugoujon, Jean-Michel

    2012-01-01

    The Hmong Diaspora is one of the widest modern human migrations. Mainly localised in South-East Asia, the United States of America, and metropolitan France, a small community has also settled the Amazonian forest of French Guiana. We have biologically analysed 62 individuals of this unique Guianese population through three complementary genetic markers: mitochondrial DNA (HVS-I/II and coding region SNPs), Y-chromosome (SNPs and STRs), and the Gm allotypic system. All genetic systems showed a high conservation of the Asian gene pool (Asian ancestry: mtDNA=100.0%; NRY=99.1%; Gm=96.6%), without a trace of founder effect. When compared across various Asian populations, the highest correlations were observed with Hmong-Mien groups still living in South-East Asia (Fst<0.05; P-value<0.05). Despite a long history punctuated by exodus, the French Guianese Hmong have maintained their original genetic diversity.

  2. Environmental Stressors, Low Well-being, Smoking, and Alcohol Use Among South African Adolescents

    PubMed Central

    Brook, David W.; Rubenstone, Elizabeth; Zhang, Chenshu; Morojele, Neo K.; Brook, Judith S.

    2011-01-01

    This is the first study to examine the pathways from environmental stressors to substance use among a sample of South African adolescents (N=2,195). The study objective was to assess how environmental stressors might affect cigarette smoking and alcohol use among South African adolescents, and to focus on one mechanism, low well-being, which might mediate this association. Participants consisted of 2,195 Black, mixed ancestry (“Coloured”), Indian, and White youth, aged 12 to 17 years old (mean age=14.6; SD=1.8), recruited via a multi-stage stratified sampling procedure in Durban, Cape Town, and Johannesburg, South Africa. Data were collected via individual in-person structured interviews, administered by trained interviewers in the participant’s preferred language. Structural equation modeling was used to analyze the interrelationships of environmental stressors (violent victimisation, legal and illegal drug availability) and low well-being (depressive symptoms, low self-esteem, health problems) with respect to adolescent cigarette smoking and alcohol use. The results supported our hypotheses: Environmental stressors were related to low well-being which, in turn, was linked to both adolescent smoking and alcohol use. There were also direct pathways from environmental stressors to both adolescent smoking and alcohol use. Smoking and alcohol use were significantly correlated. The findings suggest that environmental stressors may be associated with diminished psychological and physical well-being, as well as smoking and alcohol use, among South African adolescents. Longitudinal research is warranted to further understand the interrelationship of environmental stressors, low well-being, and adolescent substance use, so that these issues may be addressed by South African programmes and policies. PMID:21492977

  3. Heterozygosity for Tay-Sachs and Sandhoff diseases in non-Jewish Americans with ancestry from Ireland, Great Britain, or Italy.

    PubMed

    Branda, Kelly Johnston; Tomczak, Jerzy; Natowicz, Marvin R

    2004-01-01

    Previous reports have found that non-Jewish Americans with ancestry from Ireland have an increased frequency of heterozygosity for Tay-Sachs disease (TSD), although frequency estimates are substantially different. Our goal in this study was to determine the frequency of heterozygosity for TSD and Sandhoff diseases (SD) among Irish Americans, as well as in persons of English, Scottish, and/or Welsh ancestry and in individuals with Italian heritage, who were referred for determination of their heterozygosity status and who had no known family history of TSD or SD or of heterozygosity for these conditions. Of 610 nonpregnant subjects with Irish background, 24 TSD heterozygotes were identified by biochemical testing, corresponding to a heterozygote frequency of 1 in 25 (4%; 95% CI, 1/39-1/17). In comparison, of 322 nonpregnant individuals with ancestry from England, Scotland, or Wales, two TSD heterozygotes were identified (1 in 161 or 0.62%; 95% CI, 1/328-1/45), and three TSD heterozygotes were ascertained from 436 nonpregnant individuals with Italian heritage (1 in 145 or 0.69%; 95% CI, 1/714-1/50). Samples from 21 Irish heterozygotes were analyzed for HEXA gene mutations. Two (9.5%) Irish heterozygotes had the lethal + 1 IVS-9 G --> A mutation, whereas 9 (42.8%) had a benign pseudodeficiency mutation. No mutation was found in 10 (47.6%) heterozygotes. These data allow for a frequency estimate of deleterious alleles for TSD among Irish Americans of 1 in 305 (95% CI, 1/2517-1/85) to 1 in 41 (95% CI, 1/72-1/35), depending on whether one, respectively, excludes or includes enzyme-defined heterozygotes lacking a defined deleterious mutation. Pseudodeficiency mutations were identified in both of the heterozygotes with ancestry from other countries in the British Isles, suggesting that individuals with ancestry from these countries do not have an increased rate of TSD heterozygosity. Four SD heterozygotes were found among individuals of Italian descent, a frequency of 1 in

  4. Rationale, design, and baseline findings from HIPP: A randomized controlled trial testing a Home-based, Individually-tailored Physical activity Print intervention for African American women in the Deep South

    PubMed Central

    Pekmezi, Dori; Ainsworth, Cole; Joseph, Rodney; Bray, Molly S.; Kvale, Elizabeth; Isaac, Shiney; Desmond, Renee; Meneses, Karen; Marcus, Bess; Demark-Wahnefried, Wendy

    2016-01-01

    African American women report high rates of physical inactivity and related health disparities. In our previous formative research, we conducted a series of qualitative assessments to examine physical activity barriers and intervention preferences among African American women in the Deep South. These data were used to inform a 12-month Home-based, Individually-tailored Physical activity Print (HIPP) intervention, which is currently being evaluated against a wellness contact control condition among 84 post-menopausal African American women residing in the metropolitan area of Birmingham, Alabama. This paper reports the rationale, design and baseline findings of the HIPP trial. The accrued participants had an average age of 57 (SD= 4.7), a BMI of 32.1 kg/m2 (SD=5.16) with more than half (55%) having a college education and an annual household income under $50,000 (53.6%). At baseline, participants reported an average of 41.5 minutes/week (SD=49.7) of moderate intensity physical activity, and 94.1% were in the contemplation or preparation stages of readiness for physical activity. While social support for exercise from friends and family was low, baseline levels of self-efficacy, cognitive and behavioral processes of change, decisional balance, outcome expectations, and enjoyment appeared promising. Baseline data indicated high rates of obesity and low levels of physical activity, providing strong evidence of need for intervention. Moreover, scores on psychosocial measures suggested that such efforts may be well received. This line of research in technology-based approaches for promoting physical activity in African American women in the Deep South has great potential to address health disparities and impact public health. PMID:26944022

  5. Rationale, design, and baseline findings from HIPP: A randomized controlled trial testing a home-based, individually-tailored physical activity print intervention for African American women in the Deep South.

    PubMed

    Pekmezi, Dori; Ainsworth, Cole; Joseph, Rodney; Bray, Molly S; Kvale, Elizabeth; Isaac, Shiney; Desmond, Renee; Meneses, Karen; Marcus, Bess; Demark-Wahnefried, Wendy

    2016-03-01

    African American women report high rates of physical inactivity and related health disparities. In our previous formative research, we conducted a series of qualitative assessments to examine physical activity barriers and intervention preferences among African American women in the Deep South. These data were used to inform a 12-month Home-based, Individually-tailored Physical activity Print (HIPP) intervention, which is currently being evaluated against a wellness contact control condition among 84 post-menopausal African American women residing in the metropolitan area of Birmingham, Alabama. This paper reports the rationale, design and baseline findings of the HIPP trial. The accrued participants had an average age of 57 (SD=4.7), a BMI of 32.1 kg/m(2) (SD=5.16) with more than half (55%) having a college education and an annual household income under $50,000 (53.6%). At baseline, participants reported an average of 41.5 min/week (SD=49.7) of moderate intensity physical activity, and 94.1% were in the contemplation or preparation stages of readiness for physical activity. While social support for exercise from friends and family was low, baseline levels of self-efficacy, cognitive and behavioral processes of change, decisional balance, outcome expectations, and enjoyment appeared promising. Baseline data indicated high rates of obesity and low levels of physical activity, providing strong evidence of need for intervention. Moreover, scores on psychosocial measures suggested that such efforts may be well received. This line of research in technology-based approaches for promoting physical activity in African American women in the Deep South has great potential to address health disparities and impact public health.

  6. A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies.

    PubMed

    Bodea, Corneliu A; Neale, Benjamin M; Ripke, Stephan; Daly, Mark J; Devlin, Bernie; Roeder, Kathryn

    2016-05-05

    One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data.

  7. A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies

    PubMed Central

    Bodea, Corneliu A.; Neale, Benjamin M.; Ripke, Stephan; Barclay, Murray; Peyrin-Biroulet, Laurent; Chamaillard, Mathias; Colombel, Jean-Frederick; Cottone, Mario; Croft, Anthony; D’Incà, Renata; Halfvarson, Jonas; Hanigan, Katherine; Henderson, Paul; Hugot, Jean-Pierre; Karban, Amir; Kennedy, Nicholas A.; Khan, Mohammed Azam; Lémann, Marc; Levine, Arie; Massey, Dunecan; Milla, Monica; Montgomery, Grant W.; Ng, Sok Meng Evelyn; Oikonomou, Ioannis; Peeters, Harald; Proctor, Deborah D.; Rahier, Jean-Francois; Roberts, Rebecca; Rutgeerts, Paul; Seibold, Frank; Stronati, Laura; Taylor, Kirstin M.; Törkvist, Leif; Ublick, Kullak; Van Limbergen, Johan; Van Gossum, Andre; Vatn, Morten H.; Zhang, Hu; Zhang, Wei; Andrews, Jane M.; Bampton, Peter A.; Barclay, Murray; Florin, Timothy H.; Gearry, Richard; Krishnaprasad, Krupa; Lawrance, Ian C.; Mahy, Gillian; Montgomery, Grant W.; Radford-Smith, Graham; Roberts, Rebecca L.; Simms, Lisa A.; Amininijad, Leila; Cleynen, Isabelle; Dewit, Olivier; Franchimont, Denis; Georges, Michel; Laukens, Debby; Peeters, Harald; Rahier, Jean-Francois; Rutgeerts, Paul; Theatre, Emilie; Van Gossum, André; Vermeire, Severine; Aumais, Guy; Baidoo, Leonard; Barrie, Arthur M.; Beck, Karen; Bernard, Edmond-Jean; Binion, David G.; Bitton, Alain; Brant, Steve R.; Cho, Judy H.; Cohen, Albert; Croitoru, Kenneth; Daly, Mark J.; Datta, Lisa W.; Deslandres, Colette; Duerr, Richard H.; Dutridge, Debra; Ferguson, John; Fultz, Joann; Goyette, Philippe; Greenberg, Gordon R.; Haritunians, Talin; Jobin, Gilles; Katz, Seymour; Lahaie, Raymond G.; McGovern, Dermot P.; Nelson, Linda; Ng, Sok Meng; Ning, Kaida; Oikonomou, Ioannis; Paré, Pierre; Proctor, Deborah D.; Regueiro, Miguel D.; Rioux, John D.; Ruggiero, Elizabeth; Schumm, L. Philip; Schwartz, Marc; Scott, Regan; Sharma, Yashoda; Silverberg, Mark S.; Spears, Denise; Steinhart, A. Hillary; Stempak, Joanne M.; Swoger, Jason M.; Tsagarelis, Constantina; Zhang, Wei; Zhang, Clarence; Zhao, Hongyu; Aerts, Jan; Ahmad, Tariq; Arbury, Hazel; Attwood, Anthony; Auton, Adam; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Chris; Barrett, Jeffrey C.; Barroso, Inês; Barton, Anne; Bennett, Amanda J.; Bhaskar, Sanjeev; Blaszczyk, Katarzyna; Bowes, John; Brand, Oliver J.; Braund, Peter S.; Bredin, Francesca; Breen, Gerome; Brown, Morris J.; Bruce, Ian N.; Bull, Jaswinder; Burren, Oliver S.; Burton, John; Byrnes, Jake; Caesar, Sian; Cardin, Niall; Clee, Chris M.; Coffey, Alison J.; Connell, John M.C.; Conrad, Donald F.; Cooper, Jason D.; Dominiczak, Anna F.; Downes, Kate; Drummond, Hazel E.; Dudakia, Darshna; Dunham, Andrew; Ebbs, Bernadette; Eccles, Diana; Edkins, Sarah; Edwards, Cathryn; Elliot, Anna; Emery, Paul; Evans, David M.; Evans, Gareth; Eyre, Steve; Farmer, Anne; Ferrier, Nicol; Flynn, Edward; Forbes, Alistair; Forty, Liz; Franklyn, Jayne A.; Frayling, Timothy M.; Freathy, Rachel M.; Giannoulatou, Eleni; Gibbs, Polly; Gilbert, Paul; Gordon-Smith, Katherine; Gray, Emma; Green, Elaine; Groves, Chris J.; Grozeva, Detelina; Gwilliam, Rhian; Hall, Anita; Hammond, Naomi; Hardy, Matt; Harrison, Pile; Hassanali, Neelam; Hebaishi, Husam; Hines, Sarah; Hinks, Anne; Hitman, Graham A.; Hocking, Lynne; Holmes, Chris; Howard, Eleanor; Howard, Philip; Howson, Joanna M.M.; Hughes, Debbie; Hunt, Sarah; Isaacs, John D.; Jain, Mahim; Jewell, Derek P.; Johnson, Toby; Jolley, Jennifer D.; Jones, Ian R.; Jones, Lisa A.; Kirov, George; Langford, Cordelia F.; Lango-Allen, Hana; Lathrop, G. Mark; Lee, James; Lee, Kate L.; Lees, Charlie; Lewis, Kevin; Lindgren, Cecilia M.; Maisuria-Armer, Meeta; Maller, Julian; Mansfield, John; Marchini, Jonathan L.; Martin, Paul; Massey, Dunecan C.O.; McArdle, Wendy L.; McGuffin, Peter; McLay, Kirsten E.; McVean, Gil; Mentzer, Alex; Mimmack, Michael L.; Morgan, Ann E.; Morris, Andrew P.; Mowat, Craig; Munroe, Patricia B.; Myers, Simon; Newman, William; Nimmo, Elaine R.; O’Donovan, Michael C.; Onipinla, Abiodun; Ovington, Nigel R.; Owen, Michael J.; Palin, Kimmo; Palotie, Aarno; Parnell, Kirstie; Pearson, Richard; Pernet, David; Perry, John R.B.; Phillips, Anne; Plagnol, Vincent; Prescott, Natalie J.; Prokopenko, Inga; Quail, Michael A.; Rafelt, Suzanne; Rayner, Nigel W.; Reid, David M.; Renwick, Anthony; Ring, Susan M.; Robertson, Neil; Robson, Samuel; Russell, Ellie; St Clair, David; Sambrook, Jennifer G.; Sanderson, Jeremy D.; Sawcer, Stephen J.; Schuilenburg, Helen; Scott, Carol E.; Scott, Richard; Seal, Sheila; Shaw-Hawkins, Sue; Shields, Beverley M.; Simmonds, Matthew J.; Smyth, Debbie J.; Somaskantharajah, Elilan; Spanova, Katarina; Steer, Sophia; Stephens, Jonathan; Stevens, Helen E.; Stirrups, Kathy; Stone, Millicent A.; Strachan, David P.; Su, Zhan; Symmons, Deborah P.M.; Thompson, John R.; Thomson, Wendy; Tobin, Martin D.; Travers, Mary E.; Turnbull, Clare; Vukcevic, Damjan; Wain, Louise V.; Walker, Mark; Walker, Neil M.; Wallace, Chris; Warren-Perry, Margaret; Watkins, Nicholas A.; Webster, John; Weedon, Michael N.; Wilson, Anthony G.; Woodburn, Matthew; Wordsworth, B. Paul; Yau, Chris; Young, Allan H.; Zeggini, Eleftheria; Brown, Matthew A.; Burton, Paul R.; Caulfield, Mark J.; Compston, Alastair; Farrall, Martin; Gough, Stephen C.L.; Hall, Alistair S.; Hattersley, Andrew T.; Hill, Adrian V.S.; Mathew, Christopher G.; Pembrey, Marcus; Satsangi, Jack; Stratton, Michael R.; Worthington, Jane; Hurles, Matthew E.; Duncanson, Audrey; Ouwehand, Willem H.; Parkes, Miles; Rahman, Nazneen; Todd, John A.; Samani, Nilesh J.; Kwiatkowski, Dominic P.; McCarthy, Mark I.; Craddock, Nick; Deloukas, Panos; Donnelly, Peter; Blackwell, Jenefer M.; Bramon, Elvira; Casas, Juan P.; Corvin, Aiden; Jankowski, Janusz; Markus, Hugh S.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Daly, Mark J.; Devlin, Bernie; Roeder, Kathryn

    2016-01-01

    One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data. PMID:27087321

  8. Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.

    PubMed

    Kim, Sungeun; Nho, Kwangsik; Ramanan, Vijay K; Lai, Dongbing; Foroud, Tatiana M; Lane, Katie; Murrell, Jill R; Gao, Sujuan; Hall, Kathleen S; Unverzagt, Frederick W; Baiyewu, Olusegun; Ogunniyi, Adesola; Gureje, Oye; Kling, Mitchel A; Doraiswamy, P Murali; Kaddurah-Daouk, Rima; Hendrie, Hugh C; Saykin, Andrew J

    2016-01-01

    Plasma homocysteine, a metabolite involved in key cellular methylation processes seems to be implicated in cognitive functions and cardiovascular health with its high levels representing a potential modifiable risk factor for Alzheimer's disease (AD) and other dementias. A better understanding of the genetic factors regulating homocysteine levels, particularly in non-white populations, may help in risk stratification analyses of existing clinical trials and may point to novel targets for homocysteine-lowering therapy. To identify genetic influences on plasma homocysteine levels in individuals with African ancestry, we performed a targeted gene and pathway-based analysis using a priori biological information and then to identify new association performed a genome-wide association study. All analyses used combined data from the African American and Yoruba cohorts from the Indianapolis-Ibadan Dementia Project. Targeted analyses demonstrated significant associations of homocysteine and variants within the CBS (Cystathionine beta-Synthase) gene. We identified a novel genome-wide significant association of the AD risk gene CD2AP (CD2-associated protein) with plasma homocysteine levels in both cohorts. Minor allele (T) carriers of identified CD2AP variant (rs6940729) exhibited decreased homocysteine level. Pathway enrichment analysis identified several interesting pathways including the GABA receptor activation pathway. This is noteworthy given the known antagonistic effect of homocysteine on GABA receptors. These findings identify several new targets warranting further investigation in relation to the role of homocysteine in neurodegeneration.

  9. JC polyoma virus interacts with APOL1 in African Americans with nondiabetic nephropathy.

    PubMed

    Divers, Jasmin; Núñez, Marina; High, Kevin P; Murea, Mariana; Rocco, Michael V; Ma, Lijun; Bowden, Donald W; Hicks, Pamela J; Spainhour, Mitzie; Ornelles, David A; Kleiboeker, Steven B; Duncan, Kara; Langefeld, Carl D; Turner, Jolyn; Freedman, Barry I

    2013-12-01

    Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.

  10. Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ε4, and the Risk of Late-Onset Alzheimer Disease in African Americans

    PubMed Central

    Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hendrie, Hugh; Hall, Kathleen S.; Goate, Alison M.; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Mayeux, Richard

    2013-01-01

    Importance Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, Setting, and Participants The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance–weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main Outcomes and Measures Presence of Alzheimer disease according to standardized criteria. Results Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10–9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8

  11. Admixture mapping of lung cancer in 1812 African-Americans.

    PubMed

    Schwartz, Ann G; Wenzlaff, Angela S; Bock, Cathryn H; Ruterbusch, Julie J; Chen, Wei; Cote, Michele L; Artis, Amanda S; Van Dyke, Alison L; Land, Susan J; Harris, Curtis C; Pine, Sharon R; Spitz, Margaret R; Amos, Christopher I; Levin, Albert M; McKeigue, Paul M

    2011-03-01

    Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most recently genome-wide association studies (GWAS). The African-American population has been underrepresented in these genetic studies and has patterns of cigarette use and linkage disequilibrium that differ from patterns in other populations. Therefore, studies in African-Americans can provide complementary data to localize lung cancer susceptibility genes and explore smoking dependence-related genes. We used admixture mapping to further characterize genetic risk of lung cancer in a series of 837 African-American lung cancer cases and 975 African-American controls genotyped at 1344 ancestry informative single-nucleotide polymorphisms. Both case-only and case-control analyses were conducted using ADMIXMAP adjusted for age, sex, pack-years of smoking, family history of lung cancer, history of emphysema and study site. In case-only analyses, excess European ancestry was observed over a wide region on chromosome 1 with the largest excess seen at rs6587361 for non-small-cell lung cancer (NSCLC) (Z-score = -4.33; P = 1.5 × 10⁻⁵) and for women with NSCLC (Z-score = -4.82; P = 1.4 × 10⁻⁶). Excess African ancestry was also observed on chromosome 3q with a peak Z-score of 3.33 (P = 0.0009) at rs181696 among ever smokers with NSCLC. These results add to the findings from the GWAS in Caucasian populations and suggest novel regions of interest.

  12. Analysis of iris surface features in populations of diverse ancestry

    PubMed Central

    Edwards, Melissa; Cha, David; Krithika, S.; Johnson, Monique; Parra, Esteban J.

    2016-01-01

    There are many textural elements that can be found in the human eye, including Fuchs’ crypts, Wolfflin nodules, pigment spots, contraction furrows and conjunctival melanosis. Although iris surface features have been well-studied in populations of European ancestry, the worldwide distribution of these traits is poorly understood. In this paper, we develop a new method of characterizing iris features from photographs of the iris. We then apply this method to a diverse sample of East Asian, European and South Asian ancestry. All five iris features showed significant differences in frequency between the three populations, indicating that iris features are largely population dependent. Although none of the features were correlated with each other in the East and South Asian groups, Fuchs’ crypts were significantly correlated with contraction furrows and pigment spots and contraction furrows were significantly associated with pigment spots in the European group. The genetic marker SEMA3A rs10235789 was significantly associated with Fuchs’ crypt grade in the European, East Asian and South Asian samples and a borderline association between TRAF3IP1 rs3739070 and contraction furrow grade was found in the European sample. The study of iris surface features in diverse populations may provide valuable information of forensic, biomedical and ophthalmological interest. PMID:26909168

  13. ObStruct: a method to objectively analyse factors driving population structure using Bayesian ancestry profiles.

    PubMed

    Gayevskiy, Velimir; Klaere, Steffen; Knight, Sarah; Goddard, Matthew R

    2014-01-01

    Bayesian inference methods are extensively used to detect the presence of population structure given genetic data. The primary output of software implementing these methods are ancestry profiles of sampled individuals. While these profiles robustly partition the data into subgroups, currently there is no objective method to determine whether the fixed factor of interest (e.g. geographic origin) correlates with inferred subgroups or not, and if so, which populations are driving this correlation. We present ObStruct, a novel tool to objectively analyse the nature of structure revealed in Bayesian ancestry profiles using established statistical methods. ObStruct evaluates the extent of structural similarity between sampled and inferred populations, tests the significance of population differentiation, provides information on the contribution of sampled and inferred populations to the observed structure and crucially determines whether the predetermined factor of interest correlates with inferred population structure. Analyses of simulated and experimental data highlight ObStruct's ability to objectively assess the nature of structure in populations. We show the method is capable of capturing an increase in the level of structure with increasing time since divergence between simulated populations. Further, we applied the method to a highly structured dataset of 1,484 humans from seven continents and a less structured dataset of 179 Saccharomyces cerevisiae from three regions in New Zealand. Our results show that ObStruct provides an objective metric to classify the degree, drivers and significance of inferred structure, as well as providing novel insights into the relationships between sampled populations, and adds a final step to the pipeline for population structure analyses.

  14. Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

    PubMed

    Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

    2013-01-01

    The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago.

  15. Disparate Vitamin D Activity in the Prostate of Men with African Ancestry

    DTIC Science & Technology

    2015-10-01

    D3 deficiency increases PCa mortality, highlighting the importance of maintaining adequate vitamin D3 status for prostate health. Vitamin D3 is...synthesis in darker pigmented skin. Consequently, ~65% of AA men are vitamin D3 deficient compared to ~20% of EA men. The level of skin pigmentation is...PCa and death from PCa. Vitamin D3 deficiency increases PCa mortality, highlighting the importance of maintaining adequate vitamin D3 status for

  16. Disparate Vitamin D Activity in the Prostate of Men with African Ancestry

    DTIC Science & Technology

    2014-10-01

    aggressive PCa and death from PCa. Vitamin D3 deficiency increases PCa mortality, highlighting the importance of maintaining adequate vitamin D3 status...radiation, which leads to reduced vitamin D3 synthesis in darker pigmented skin. Consequently, ~65% of AA men are vitamin D3 deficient compared to ~20% of... deficiency increases PCa mortality, highlighting the importance of maintaining adequate vitamin D3 status for prostate health. Vitamin D3 is

  17. Education of Non-European Ancestry Immigrant Students in Suburban High Schools

    ERIC Educational Resources Information Center

    Shodavaram, Mary P.; Jones, Lisa A.; Weaver, Laurie R.; Marquez, Judith A.; Ensle, Anne L.

    2009-01-01

    The purpose of this study was to examine suburban high school teachers' beliefs about non-European ancestry immigrant students; more specifically, suburban teachers' beliefs regarding the impact of students' cultural backgrounds on academic performance were examined. Non-European ancestry immigrant students are those students whose ancestral…

  18. Measurement Uncertainty in Racial and Ethnic Identification among Adolescents of Mixed Ancestry: A Latent Variable Approach

    ERIC Educational Resources Information Center

    Tracy, Allison J.; Erkut, Sumru; Porche, Michelle V.; Kim, Jo; Charmaraman, Linda; Grossman, Jennifer M.; Ceder, Ineke; Garcia, Heidie Vazquez

    2010-01-01

    In this article, we operationalize identification of mixed racial and ethnic ancestry among adolescents as a latent variable to (a) account for measurement uncertainty, and (b) compare alternative wording formats for racial and ethnic self-categorization in surveys. Two latent variable models were fit to multiple mixed-ancestry indicator data from…

  19. A comprehensive examination of breast cancer risk loci in African American women

    PubMed Central

    Feng, Ye; Stram, Daniel O.; Rhie, Suhn Kyong; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F.; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; Palmer, Julie R.; Olopade, Olufunmilayo I.; Huo, Dezheng; Adebamowo, Clement A.; Ogundiran, Temidayo; Chen, Gary K.; Stram, Alex; Park, Karen; Rand, Kristin A.; Chanock, Stephen J.; Le Marchand, Loic; Kolonel, Laurence N.; Conti, David V.; Easton, Douglas; Henderson, Brian E.; Haiman, Christopher A.

    2014-01-01

    Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10−6) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65–70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry. PMID:24852375

  20. Race and Ancestry in the Age of Inclusion: Technique and Meaning in Post-Genomic Science

    PubMed Central

    Shim, Janet K.; Ackerman, Sara L.; Darling, Katherine Weatherford; Hiatt, Robert A.; Lee, Sandra Soo-Jin

    2015-01-01

    This paper examines how race and ancestry are taken up in gene-environment interaction (GEI) research on complex diseases such as heart disease, diabetes, and cancer. Using 54 in-depth interviews of 33 scientists and over 200 hours of observation at scientific conferences, we explore how GEI researchers use and interpret race, ethnicity, and ancestry in their work. We find that the use of self-identified race and ethnicity (SIRE) exists alongside ancestry informative markers (AIMs) to ascertain genetic ancestry. Our participants assess the utility of these two techniques in relative terms, downplaying the accuracy and value of SIRE compared to the precision and necessity of AIMs. In doing so, we argue that post-genomic scientists seeking to understand the interactions of genetic and environmental disease determinants actually undermine their ability to do so, by valorizing precise characterizations of individuals’ genetic ancestry over measurement of the social processes and relations that differentiate social groups. PMID:25378251

  1. Replication of GWAS "Hits" by Race for Breast and Prostate Cancers in European Americans and African Americans.

    PubMed

    Barnholtz-Sloan, Jill S; Raska, Paola; Rebbeck, Timothy R; Millikan, Robert C

    2011-01-01

    In this study, we assessed association of genome-wide association studies (GWAS) "hits" by race with adjustment for potential population stratification (PS) in two large, diverse study populations; the Carolina Breast Cancer Study (CBCS; N total = 3693 individuals) and the University of Pennsylvania Study of Clinical Outcomes, Risk, and Ethnicity (SCORE; N total = 1135 individuals). In both study populations, 136 ancestry information markers and GWAS "hits" (CBCS: FGFR2, 8q24; SCORE: JAZF1, MSMB, 8q24) were genotyped. Principal component analysis was used to assess ancestral differences by race. Multivariable unconditional logistic regression was used to assess differences in cancer risk with and without adjustment for the first ancestral principal component (PC1) and for an interaction effect between PC1 and the GWAS "hit" (SNP) of interest. PC1 explained 53.7% of the variance for CBCS and 49.5% of the variance for SCORE. European Americans and African Americans were similar in their ancestral structure between CBCS and SCORE and cases and controls were well matched by ancestry. In the CBCS European Americans, 9/11 SNPs were significant after PC1 adjustment, but after adjustment for the PC1 by SNP interaction effect, only one SNP remained significant (rs1219648 in FGFR2); for CBCS African Americans, 6/11 SNPs were significant after PC1 adjustment and after adjustment for the PC1 by SNP interaction effect, all six SNPs remained significant and an additional SNP now became significant. In the SCORE European Americans, 0/9 SNPs were significant after PC1 adjustment and no changes were seen after additional adjustment for the PC1 by SNP interaction effect; for SCORE African Americans, 2/9 SNPs were significant after PC1 adjustment and after adjustment for the PC1 by SNP interaction effect, only one SNP remained significant (rs16901979 at 8q24). We show that genetic associations by race are modified by interaction between individual SNPs and PS.

  2. Replication of GWAS “Hits” by Race for Breast and Prostate Cancers in European Americans and African Americans

    PubMed Central

    Barnholtz-Sloan, Jill S.; Raska, Paola; Rebbeck, Timothy R.; Millikan, Robert C.

    2011-01-01

    In this study, we assessed association of genome-wide association studies (GWAS) “hits” by race with adjustment for potential population stratification (PS) in two large, diverse study populations; the Carolina Breast Cancer Study (CBCS; N total = 3693 individuals) and the University of Pennsylvania Study of Clinical Outcomes, Risk, and Ethnicity (SCORE; N total = 1135 individuals). In both study populations, 136 ancestry information markers and GWAS “hits” (CBCS: FGFR2, 8q24; SCORE: JAZF1, MSMB, 8q24) were genotyped. Principal component analysis was used to assess ancestral differences by race. Multivariable unconditional logistic regression was used to assess differences in cancer risk with and without adjustment for the first ancestral principal component (PC1) and for an interaction effect between PC1 and the GWAS “hit” (SNP) of interest. PC1 explained 53.7% of the variance for CBCS and 49.5% of the variance for SCORE. European Americans and African Americans were similar in their ancestral structure between CBCS and SCORE and cases and controls were well matched by ancestry. In the CBCS European Americans, 9/11 SNPs were significant after PC1 adjustment, but after adjustment for the PC1 by SNP interaction effect, only one SNP remained significant (rs1219648 in FGFR2); for CBCS African Americans, 6/11 SNPs were significant after PC1 adjustment and after adjustment for the PC1 by SNP interaction effect, all six SNPs remained significant and an additional SNP now became significant. In the SCORE European Americans, 0/9 SNPs were significant after PC1 adjustment and no changes were seen after additional adjustment for the PC1 by SNP interaction effect; for SCORE African Americans, 2/9 SNPs were significant after PC1 adjustment and after adjustment for the PC1 by SNP interaction effect, only one SNP remained significant (rs16901979 at 8q24). We show that genetic associations by race are modified by interaction between individual SNPs and PS

  3. Population Genomics of sub-saharan Drosophila melanogaster: African diversity and non-African admixture.

    PubMed

    Pool, John E; Corbett-Detig, Russell B; Sugino, Ryuichi P; Stevens, Kristian A; Cardeno, Charis M; Crepeau, Marc W; Duchen, Pablo; Emerson, J J; Saelao, Perot; Begun, David J; Langley, Charles H

    2012-01-01

    Drosophila melanogaster has played a pivotal role in the development of modern population genetics. However, many basic questions regarding the demographic and adaptive history of this species remain unresolved. We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection within an African population, between African populations, and between European and African populations. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa F(ST) were found to be enriched in genomic regions of locally elevated

  4. Individual and Partner-Level Factors Associated with Condom Non-Use Among African American STI Clinic Attendees in the Deep South: An Event-Level Analysis.

    PubMed

    Marshall, Brandon D L; Perez-Brumer, Amaya G; MacCarthy, Sarah; Mena, Leandro; Chan, Philip A; Towey, Caitlin; Barnett, Nancy; Parker, Sharon; Barnes, Arti; Brinkley-Rubinstein, Lauren; Rose, Jennifer S; Nunn, Amy S

    2016-06-01

    The US HIV/AIDS epidemic is concentrated in the Deep South, yet factors contributing to HIV transmission are not fully understood. We examined relationships between substance use, sexual partnership characteristics, and condom non-use in an African American sample of STI clinic attendees in Jackson, Mississippi. We assessed condom non-use at last intercourse with up to three recent sexual partners reported by participants between January and June 2011. Participant- and partner-level correlates of condom non-use were examined using generalized estimating equations. The 1295 participants reported 2880 intercourse events, of which 1490 (51.7 %) involved condom non-use. Older age, lower educational attainment, reporting financial or material dependence on a sex partner, sex with a primary partner, and higher frequency of sex were associated with increased odds of condomless sex. HIV prevention efforts in the South should address underlying socioeconomic disparities and structural determinants that result in partner dependency and sexual risk behavior.

  5. The cancer caregiving experience of caregivers of Mexican ancestry.

    PubMed

    Juarez, Gloria; Branin, Joan J; Rosales, Monica

    2014-01-01

    The act of providing care may be the same in all ethnic groups, but the way caregiving is defined by family members is influenced by cultural values and beliefs. This study describes the caregiving experience and challenges of caregivers of Mexican ancestry. Qualitative interviews of 20 family caregivers and thematic analysis of transcribed audiotapes identified four themes that characterized their caregiving experience. These themes include an emphasis on family values, a strong commitment to care, difficulties dealing with everyday life realities, and a reliance on spirituality, all of which added to the meaningfulness and burden of caregiving. Further investigation within a cultural context is warranted in the development of interventions and programs to better assist caregivers in coping with the challenges of providing cancer care.

  6. Spread of pedigree versus genetic ancestry in spatially distributed populations.

    PubMed

    Kelleher, J; Etheridge, A M; Véber, A; Barton, N H

    2016-04-01

    Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ∼ t rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models.

  7. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

    PubMed Central

    Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I.; Conti, David V.; Schumacher, Fredrick; Han, Ying; Benlloch, Sara; Hazelett, Dennis J.; Wang, Zhaoming; Saunders, Ed; Leongamornlert, Daniel; Lindstrom, Sara; Jugurnauth-Little, Sara; Dadaev, Tokhir; Tymrakiewicz, Malgorzata; Stram, Daniel O.; Rand, Kristin; Wan, Peggy; Stram, Alex; Sheng, Xin; Pooler, Loreall C.; Park, Karen; Xia, Lucy; Tyrer, Jonathan; Kolonel, Laurence N.; Le Marchand, Loic; Hoover, Robert N.; Machiela, Mitchell J.; Yeager, Merideth; Burdette, Laurie; Chung, Charles C.; Hutchinson, Amy; Yu, Kai; Goh, Chee; Ahmed, Mahbubl; Govindasami, Koveela; Guy, Michelle; Tammela, Teuvo L.J.; Auvinen, Anssi; Wahlfors, Tiina; Schleutker, Johanna; Visakorpi, Tapio; Leinonen, Katri A.; Xu, Jianfeng; Aly, Markus; Donovan, Jenny; Travis, Ruth C.; Key, Tim J.; Siddiq, Afshan; Canzian, Federico; Khaw, Kay-Tee; Takahashi, Atsushi; Kubo, Michiaki; Pharoah, Paul; Pashayan, Nora; Weischer, Maren; Nordestgaard, Borge G.; Nielsen, Sune F.; Klarskov, Peter; Røder, Martin Andreas; Iversen, Peter; Thibodeau, Stephen N.; McDonnell, Shannon K; Schaid, Daniel J; Stanford, Janet L.; Kolb, Suzanne; Holt, Sarah; Knudsen, Beatrice; Coll, Antonio Hurtado; Gapstur, Susan M.; Diver, W. Ryan; Stevens, Victoria L.; Maier, Christiane; Luedeke, Manuel; Herkommer, Kathleen; Rinckleb, Antje E.; Strom, Sara S.; Pettaway, Curtis; Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P.; Cannon-Albright, Lisa; Cybulski, Cezary; Wokołorczyk, Dominika; Kluźniak, Wojciech; Park, Jong; Sellers, Thomas; Lin, Hui-Yi; Isaacs, William B.; Partin, Alan W.; Brenner, Hermann; Dieffenbach, Aida Karina; Stegmaier, Christa; Chen, Constance; Giovannucci, Edward L.; Ma, Jing; Stampfer, Meir; Penney, Kathryn L.; Mucci, Lorelei; John, Esther M.; Ingles, Sue A.; Kittles, Rick A.; Murphy, Adam B.; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej M.; Blot, William; Signorello, Lisa B.; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, Cristina; Wu, Suh-Yuh; Hennis, Anselm; Kibel, Adam S.; Rybicki, Benjamin A.; Neslund-Dudas, Christine; Hsing, Ann W.; Chu, Lisa; Goodman, Phyllis J.; Klein, Eric A; Zheng, S. Lilly; Batra, Jyotsna; Clements, Judith; Spurdle, Amanda; Teixeira, Manuel R.; Paulo, Paula; Maia, Sofia; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Witte, John S.; Casey, Graham; Gillanders, Elizabeth M.; Seminara, Daniella; Riboli, Elio; Hamdy, Freddie C.; Coetzee, Gerhard A.; Li, Qiyuan; Freedman, Matthew L.; Hunter, David J.; Muir, Kenneth; Gronberg, Henrik; Neal, David E.; Southey, Melissa; Giles, Graham G.; Severi, Gianluca; Cook, Michael B.; Nakagawa, Hidewaki; Wiklund, Fredrik; Kraft, Peter; Chanock, Stephen J.; Henderson, Brian E.; Easton, Douglas F.; Eeles, Rosalind A.; Haiman, Christopher A.

    2014-01-01

    Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three novel susceptibility loci were revealed at P<5×10-8; 15 variants were identified among men of European ancestry, 7 from multiethnic analyses and one was associated with early-onset prostate cancer. These 23 variants, in combination with the known prostate cancer risk variants, explain 33% of the familial risk of the disease in European ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the utility of combining ancestrally diverse populations to discover risk loci for disease. PMID:25217961

  8. Population genomic analysis uncovers African and European admixture in Drosophila melanogaster populations from the south-eastern United States and Caribbean Islands.

    PubMed

    Kao, Joyce Y; Zubair, Asif; Salomon, Matthew P; Nuzhdin, Sergey V; Campo, Daniel

    2015-04-01

    Drosophila melanogaster is postulated to have colonized North America in the past several 100 years in two waves. Flies from Europe colonized the east coast United States while flies from Africa inhabited the Caribbean, which if true, make the south-east US and Caribbean Islands a secondary contact zone for African and European D. melanogaster. This scenario has been proposed based on phenotypes and limited genetic data. In our study, we have sequenced individual whole genomes of flies from populations in the south-east US and Caribbean Islands and examined these populations in conjunction with population sequences from the west coast US, Africa, and Europe. We find that west coast US populations are closely related to the European population, likely reflecting a rapid westward expansion upon first settlements into North America. We also find genomic evidence of African and European admixture in south-east US and Caribbean populations, with a clinal pattern of decreasing proportions of African ancestry with higher latitude. Our genomic analysis of D. melanogaster populations from the south-east US and Caribbean Islands provides more evidence for the Caribbean Islands as the source of previously reported novel African alleles found in other east coast US populations. We also find the border between the south-east US and the Caribbean island to be the admixture hot zone where distinctly African-like Caribbean flies become genomically more similar to European-like south-east US flies. Our findings have important implications for previous studies examining the generation of east coast US clines via selection.

  9. Use of animals with partially known ancestries in scientifically managed breeding programs.

    PubMed

    Willis, Kevin; Lacy, Robert C

    2016-07-01

    Animals with only partially known ancestry present a problem for population managers because it can be difficult to determine their relative genetic value to the population. So long as their ancestry is not completely unknown, population management software such as PMx can calculate a mean kinship for these animals, but that mean kinship is calculated such that there is no decrease in relative genetic value or "penalty" for only partially known ancestry. However, there is a longer-term genetic cost to having animals with only partially known ancestry in the population, and thus it is appropriate to "penalize" animals with partially known ancestry to some extent. The challenge is determining the correct "penalty" which will serve to decrease the percent unknown ancestry in subsequent generations while not causing excessive selection against the known ancestry of the animal. A new parameter of relative genetic value is developed which takes into account both an animal's mean kinship as well as its percent known ancestry. The method used in PMx to calculate the mean kinships also in general overestimates the inbreeding coefficients of offspring of animals with partially known ancestry when the known parents share a common ancestor, but can underestimate inbreeding if common ancestors exist within the unknown portion of the pedigree. This may result in population managers selecting less suitable pairs for breeding in an attempt to avoid an apparent higher level of inbreeding. A parameter is developed that adjusts the inbreeding coefficient to more accurately reflect the likely inbreeding coefficient of potential offspring. Zoo Biol. 35:319-325, 2016. © 2016 Wiley Periodicals, Inc.

  10. The African diaspora: mitochondrial DNA and the Atlantic slave trade.

    PubMed

    Salas, Antonio; Richards, Martin; Lareu, María-Victoria; Scozzari, Rosaria; Coppa, Alfredo; Torroni, Antonio; Macaulay, Vincent; Carracedo, Angel

    2004-03-01

    Between the 15th and 19th centuries ad, the Atlantic slave trade resulted in the forced movement of approximately 13 million people from Africa, mainly to the Americas. Only approximately 11 million survived the passage, and many more died in the early years of captivity. We have studied 481 mitochon