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
Ng MC, Graff M, Lu Y, Justice AE, Mudgal P, Liu C, Young K, Yanek LR, Feitosa MF, Wojczynski MK, Rand K, Brody JA, Cade BE, Dimitrov L, Duan Q, Guo X, Lange LA, Nalls M, Okut H, Tajuddin SM, Tayo BO, Vedantam S, Bradfield JP, Chen G, Chen W, Chesi A, Irvin MR, Padhukasahasram B, Smith JA, Zheng W, Allison MA, Ambrosone CB, Bandera E, Bartz T, Berndt S, Bernstein L, Blot W, Bottinger E, Carpten J, Chanock S, Chen Y, Conti D, Cooper R, Fornage M, Freedman B, Garcia M, Goodman P, Hsu Y, Hu J, Huff C, Ingles S, John E, Kittles R, Klein E, Li J, McKnight B, Nayak U, Nemesure B, Ogunniyi A, Olshan A, Press M, Rohde R, Rybicki BA, Salako B, Sanderson M, Shao Y, Siscovick D, Stanford J, Stevens V, Stram A, Strom S, Vaidya D, Witte J, Yao J, Zhu X, Ziegler R, Zonderman A, Adeyemo A, Ambs S, Cushman M, Faul J, Hakonarson H, Levin AM, Nathanson K, Ware E, Weir D, Zhao W, Zhi D, Arnett D, Grant S, Kardia S, Oloapde O, Rao D, Rotimi C, Sale M, Williams KL, Zemel B, Becker D, Borecki I, Evans M, Harris T, Hirschhorn J, Li Y, Patel S, Psaty B, Rotter J, Wilson J, Bowden D, Cupples L, Haiman C, Loos R, North K. 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. PLoS Genet 2017; 13(4):1006719-1006719.
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, WHRadjBMI), 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 WHRadjBMI 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 WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI 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 WHRadjBMI (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 (
Medical Subject Headings
Adiposity; African Continental Ancestry Group; Anthropometry; Body Mass Index; Chromosome Mapping; European Continental Ancestry Group; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Linkage Disequilibrium; Male; Obesity; Polymorphism, Single Nucleotide; Serine Endopeptidases; Transcription Factor 7-Like 2 Protein; Waist-Hip Ratio