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Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHR adjBMI ), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHR adjBMI  from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus ( TCF7L2/HABP2 ) for WHR adjBMI  and eight previously established loci at  P  < 5×10 −8 : seven for BMI, and one for WHR adjBMI  in African ancestry individuals. An additional novel locus ( SPRYD7/DLEU2 ) was identified for WHR adjBMI  when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI ( INTS10/LPL  and  MLC1  in men,  IRX4/IRX2  in women) and four for WHR adjBMI  ( SSX2IP ,  CASC8 ,  PDE3B  and  ZDHHC1/HSD11B2  in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHR adjBMI  loci that were locus-wide significant ( P  < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHR adjBMI  loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHR adjBMI  including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

plos genetics

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium