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

Matthew B Lanktree, Clara C Elbers, Yun Li, Guosheng Zhang, Qing Duan, Konrad J Karczewski, Yiran Guo, Vinicius Tragante, Kari E North, Mary Cushman, Folkert W Asselbergs, James G Wilson, Leslie A Lange, Fotios Drenos, Alex P Reiner, Michael R Barnes, Brendan J Keating

Research output: Contribution to journalArticle (Academic Journal)peer-review

7 Citations (Scopus)
173 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1781-1786
Number of pages6
JournalJournal of Lipid Research
Volume56
Issue number9
Early online date21 Jul 2015
DOIs
Publication statusPublished - Sep 2015

Keywords

  • African Americans
  • Endothelium, Vascular
  • European Continental Ancestry Group
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Lipoproteins, HDL
  • Polymorphism, Single Nucleotide
  • Vesicular Transport Proteins
  • Journal Article
  • Meta-Analysis
  • Research Support, N.I.H., Extramural

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