Genome-Wide Association Study Identifies Novel Ethnic-Specific Associations With Body Mass Index

Background. Obesity affects over one-third of the US population, and is a risk factor for various chronic conditions, including type 2 diabetes, heart disease, and stroke. The disease results from a combination of behavioral and environmental risk factors and genetic predisposition. To date, over 50 genetic polymorphisms have been associated with increased body mass index (BMI), but these associations explain only a small percentage of the heritable risk of obesity. Moreover, the majority of these associations have been identified in populations of European ancestry. We sought to identify novel associations with BMI and to evaluate their generalizability across ethnic groups, using subjects from the Multi-ethnic Study of Atherosclerosis (MESA). Methods. Ethnic-specific genome-wide association analyses were conducted to identify single nucleotide polymorphisms (SNPs) associated with BMI among 1,257 Hispanic, 705 Asian, 1,551 African American, and 2,416 Caucasian MESA participants. We compared and contrasted findings across ethnic groups, and accounted for potential differences in linkage disequilibrium patterns by examining the ± 500kb flanking regions of the top SNPs in all four ethnic groups. Results. We identified one genome-wide significant association with BMI in Hispanic subjects: rs12253976 near KLF6 (p=6.88x10-09). The top SNPs in each of the other ethnic groups--rs9961691 near GATA6 in Asians (p=1.53x10-06), rs7092615 near LYZL2 in African Americans (p=2.26x10-07), and rs6866721 near SEMA6A in Caucasians (p=9.23x10-08)--may also be of interest. Each of these SNPs showed no evidence of an association with BMI in the other ethnic groups. Conclusion. We present one of the first GWAS to examine BMI-associated variants across ethnic groups in the same study. The existence of ethnic-specific associations with BMI highlights the need for future investigations in larger multiethnic cohorts. Discovery of further ethnic-specific BMI-associated loci may contribute to personalized obesity interventions