Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.
Zhang X, Brody JA, Graff M et al.
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Abstract
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Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10-9), including two secondary signals. Notably, we identified and replicated a novel low-frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.
44,540 European ancestry individuals, 22,488 African ancestry individuals, 248 Barbadian ancestry individuals, 1,241 Asian ancestry individuals, 3,840 East Asian ancestry individuals, 15,242 Hispanic or Latin American individuals, 1,274 Samoan ancestry individuals
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