Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study

Jin Li, Leslie A. Lange, Jeremy Sabourin, Qing Duan, William Valdar, Monte S. Willis, Yun Li, James G. Wilson, Ethan M. Lange

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease. Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart Study. We observed that local ancestry at 6q25.3 was an important risk factor for Lp(a) in AAs, and that multiple single-nucleotide polymorphisms (SNPs) at the well-established LPA locus were significantly associated with Lp(a) (P<5 × 10 -8) after adjusting for the local ancestry at 6q25.3. Interestingly, before adjusting for local ancestry, we observed significant (P<5 × 10 -8) associations for hundreds of SNPs spanning ∼10 Mb region on 6q surrounding the LPA gene, whereas after adjusting for local ancestry, the region containing significantly associated SNPs got much narrower and was centered over the LPA gene (<1 Mb). We observed a single nonsynonymous SNP in APOE significantly associated with Lp(a) (P<5 × 10 -8). A high burden of coding variants in LPA and APOE were also associated with higher Lp(a) levels. Our study provides evidence that ancestry-specific causal risk variant(s) resides in or near LPA and that most of the observed associations outside this narrower region are spurious associations.

Original languageEnglish (US)
Pages (from-to)755-761
Number of pages7
JournalJournal of Human Genetics
Volume60
Issue number12
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Li, J., Lange, L. A., Sabourin, J., Duan, Q., Valdar, W., Willis, M. S., Li, Y., Wilson, J. G., & Lange, E. M. (2015). Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study. Journal of Human Genetics, 60(12), 755-761. https://doi.org/10.1038/jhg.2015.107