Abstract MP068: Association Study of SNPs and measures of adiposity among 51990 European and European American Identifies Three Novel Loci

• Published in: Circulation (New York, N.Y.) N.Y.), 2012-03, Vol.125 (suppl_10)
• Main Authors: Yoneyama, Sachiko, Taylor, Kira C, Fox, Caroline S, Keating, Brendan J, Gong, Yan, Reiner, Alexander P, Shen, Haiqing, Gorski, Mathias, Padmanabhan, Sandosh, Rafelt, Suzanne, Munroe, Patricia, Lanktree, Matthew, Johnson, Toby, Gaunt, Tom R, Guo, Yiran, Speilotes, Liz, Redline, Susan, Burke, Gregory, Taylor, Herman, Ordovas, Jose, Jaquish, Cashell, Heard-Costa, Nancy, North, Kari E, Demerath, Ellen W
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.125.suppl_10.AMP068

Abstract only Introduction and objectives. Measures of adiposity such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with adverse cardiovascular events and diabetes independent of body mass index (BMI). WC and WHR have high heritability and multiple susceptibility loci have been identified across the genome, including GRB14 , LYPAL1 , and VEGFA . We aim to identify novel loci associated with WC and WHR using a bespoke SNP array focused on cardio-centric candidate genes. Methods. We assessed the association between SNPs and anthropometry phenotypes WC adjusted for BMI (cm), and WHR adjusted for BMI among 51990 individuals of European ancestry from NHLBI’s Candidate Gene Association Resource (CARe) project and 14 other cohorts. The study population consisted of women and men aged 20 to 80, of which 65% were females. Individuals were genotyped using the ITMAT/Broad/CARE (IBC) chip, which includes ∼50,000 densely mapped cosmopolitan tagged SNPs across ∼2100 candidate genes. We modeled each trait as a function of age, study site, and ancestry, and conducted a fixed-effects meta-analysis. Results. Three novel loci reached our Bonferroni adjusted threshold for statistical significance (P10%). Fine mapping is currently underway to determine whether each locus may contain multiple independent signals. Replication cohorts have been identified and we are working to verify the novel loci and investigate sub-significant loci. Conclusions . In 51990 European decent individuals typed on a dense IBC chip, we identified 3 novel loci and replicated 3 additional loci. Significant loci among WC adjusted for BMI, and WHR adjusted for BMI were distinct from one another, indicating each measure of adiposity may be captur