Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration.

Publication Type:

Journal Article

Source:

Journal of lipid research (2015)

Abstract:

Meta-analyses of European populations has successfully identified genetic variants in over 150 loci associated with lipid levels, but results from additional ethnicities remains limited. Previously, we reported two novel lipid loci identified in a sample of 7,657 African Americans using a gene-centric array including 50,000 single nucleotide polymorphisms in 2,100 candidate genes. Initial discovery and follow-up of signals with P < 10e-5 in additional African American samples confirmed CD36 and ICAM1. Using an additional 8,244 African American female samples from the Women's Health Initiative (WHI) SNP Health Association Resource (SHARe) genome-wide association study (GWAS) dataset, we further examined the previous meta-analyses results by attempting to replicate 20 additional putative lipid signals with P < 10e-4. Replication confirmed rs868213, located in a splice donor region of EXOC3L1 as a novel signal for HDL (additive allelic effect β = 0.02; P = 1.4x10e-8; meta-analyses of discovery and replication). Exocyst Complex Component 3-Like 1 (EXOC3L1) is expressed in endothelium, involved in glucose metabolism, and is a potential drug target, yielding a novel pathway for intervention in lipid traits. Increasing sample sizes for genetic studies in non-European populations will continue to improve our understanding of lipid metabolism.