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

ABSTRACT: 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.

SUBMITTER: Bhatia G

PROVIDER: S-EPMC3169818 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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

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

American journal of human genetics 20110901 3

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 set ...[more]

PMID: 21907010

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Project description: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 the concept that there are fat distribution loci that are independent of generalized adiposity.

Dataset Information

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

Publications

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

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