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

J Lipid Res. 2015 Sep;56(9):1781-6. doi: 10.1194/jlr.P059477. Epub 2015 Jul 21.

Abstract

Meta-analyses of European populations has successfully identified genetic variants in over 150 loci associated with lipid levels, but results from additional ethnicities remain 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 SNPs in 2,100 candidate genes. Initial discovery and follow-up of signals with P < 10(-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 SNP Health Association Resource genome-wide association study dataset, we further examined the previous meta-analyses results by attempting to replicate 20 additional putative lipid signals with P < 10(-4). Replication confirmed rs868213, located in a splice donor region of exocyst complex component 3-like 1 (EXOC3L1) as a novel signal for HDL (additive allelic effect β = 0.02; P = 1.4 × 10(-8); meta-analyses of discovery and replication). EXOC3L1 is strongly expressed in vascular endothelium and forms part of the exocyst complex, a key facilitator of the trafficking of lipid receptors. Increasing sample sizes for genetic studies in nonEuropean populations will continue to improve our understanding of lipid metabolism.

Keywords: exocyst complex component 3-like 1; genetics; high density lipoprotein; vascular biology.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • African Americans / genetics
  • Endothelium, Vascular / metabolism
  • European Continental Ancestry Group
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Lipoproteins, HDL / blood*
  • Lipoproteins, HDL / genetics
  • Polymorphism, Single Nucleotide
  • Vesicular Transport Proteins / genetics*

Substances

  • EXOC3 protein, human
  • Lipoproteins, HDL
  • Vesicular Transport Proteins