Abstract P233: Generalization of Adiposity-Related Common Genetic Variants among U.S. Hispanic Women in WHI-SHARe

Obesity is a global health concern. Recent studies suggest there may be shared genetic predispositions to obesity phenotypes across diverse racial and ethnic groups, yet the identification of adiposity-related genetic variants among Hispanics, now the largest minority group in the United States (U.S.), remains largely unknown. We interrogated an a priori list of 58 (41 overall body mass and 17 central adiposity) index single nucleotide polymorphisms (SNPs) previously studied in samples of European descent (ED) among 3,587 U.S. Hispanic women in the Women's Health Initiative-SNP Health Association Resource (WHI-SHARe). Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) were measured using standardized protocols. Inverse normal BMI, WC, and WHR models were adjusted for age, smoking status, study center, and genetic ancestry using principal components. Additionally WC and WHR were adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of the previously described SNP, the closest available SNP was selected as a proxy (r2≥0.3 in CEU). No SNPs reached genome-wide significance in this analysis likely due to limited power. Eight BMI/weight loci (TMEM18, ETV5, SLC39A8, NUDT3/HMGA1, FAIM2, FTO, MC4R, KCTD15) and two WC/WHR loci (VEGFA, ITPR2-SSPN) were nominally significant (p<0.05) at the reference SNP in the corresponding BMI and WC and/or WHR adjusted BMI models. To account for distinct linkage disequilibrium (LD) patterns in Hispanics and to more broadly assess generalization of genetic effects at each locus, we assessed the evidence for association at the 58 surrounding loci, for each SNP within 500 kb of the reference SNP. Two additional BMI/weight loci (FANCL, TFAP2B) and six WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86, MSRA, NRXN3) displayed statistically significant associations with BMI and waist measures after Bonferroni correction (p<0.001 and <0.003, respectively), with varying patterns of LD (r2=0.001-0.871) with the index SNP (using HapMap CEU). Sequential conditional analyses will be used to further determine if our top findings from these loci are tagging the index signal or represent novel secondary signals. In summary, we provide evidence for the generalization of ten BMI and eight central adiposity loci in Hispanic American women. This study expands the current knowledge of common adiposity-related genetic predisposition among Hispanic women in the U.S. and suggests a general relevance of ED adiposity loci to Hispanic descent individuals.