Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos

Mariaelisa Graff, Leslie S. Emery, Anne E. Justice, Esteban Parra, Jennifer E. Below, Nicholette D. Palmer, Chuan Gao, Qing Duan, Adan Valladares-Salgado, Miguel Cruz, Alanna C. Morrison, Eric Boerwinkle, Eric A. Whitsel, Charles Kooperberg, Alex Reiner, Yun Li, Carlos Jose Rodriguez, Gregory A. Talavera, Carl D. Langefeld, Lynne E. Wagenknecht, Jill M. Norris, Kent D. Taylor, George Papanicolaou, Eimear Kenny, Ruth J. F. Loos, Yii-Der Ida Chen, Cathy Laurie, Tamar Sofer, Kari E. North

Despite ethnic disparities in lipid profiles, there are few genome-wide association studies investigating genetic variation of lipids in non-European ancestry populations. In this study, we present findings from genetic association analyses for total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides in a large Hispanic/Latino cohort in the U.S., the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). We estimated a heritability of approximately 20% for each lipid trait, similar to previous estimates in Europeans. To search for novel lipid loci, we performed conditional association analysis in which the statistical model was adjusted for previously reported SNPs associated with any of the four lipid traits. SNPs that remained genome-wide significant (P < 5 × 10(-8)) after conditioning on known loci were evaluated for replication. We identified eight potentially novel lipid signals with minor allele frequencies <1%, none of which replicated. We tested previously reported SNP-trait associations for generalization to Hispanics/Latinos via a statistical framework. The generalization analysis revealed that approximately 50% of previously established lipid variants generalize to HCHS/SOL based on directional FDR r-value < 0.05. Some failures to generalize were due to lack of power. These results demonstrate that many loci associated with lipid levels are shared across populations.