Gene-centric meta-analyses for central adiposity traits in up to 57,412 individuals of European descent confirm known loci and reveal several novel associations

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes, and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57,412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20 to 80. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50,000 cosmopolitan tagged SNPs across ∼2,100 cardiovascular-related genes. Each trait was modeled as a function of age, study site, and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P