Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q

Carole Ober, Alexander Nord, Emma E. Thompson, Lin Pan, Zheng Tan, Darren Cusanovich, Ying Sun, Raluca Nicolae, Celina Edelstein, Daniel H. Schneider, Christine Billstrand, Ditta Pfaffinger, Natasha Phillips, Rebecca L. Anderson, Binu Philips, Ramakrishnan Rajagopalan, Thomas S. Hatsukami, Mark J. Rieder, Patrick J. Heagerty, Deborah A. NickersonMark Abney, Santica Marcovina, Gail P. Jarvik, Angelo M. Scanu, Dan L. Nicolae

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Plasma lipoprotein(a) (Lp[a]) level is an independent risk factor of cardiovascular disease that is under strong genetic control. We conducted a genome-wide association study of plasma Lp(a) in 386 members of a founder population that adheres to a communal lifestyle, proscribes cigarette smoking, and prepares and eats meals communally. We identified associations with 77 single nucleotide polymorphisms (SNPs) spanning 12.5 Mb on chromosome 6q26-q27 that met criteria for genome-wide significance (P ≤ 1.3 × 10-7) and were within or flanking nine genes, including LPA. We show that variation in at least six genes in addition to LPA are significantly associated with Lp(a) levels independent of each other and of the kringle IV repeat polymorphism in the LPA gene. One novel SNP in intron 37 of the LPA gene was also associated with Lp(a) levels and carotid artery disease number in unrelated Caucasians (P = 7.3 × 10-12 and 0.024, respectively), also independent of kringle IV number. This study suggests a complex genetic architecture of Lp(a) levels that may involve multiple loci on chromosome 6q26-q27.

Original languageEnglish (US)
Pages (from-to)798-806
Number of pages9
JournalJournal of Lipid Research
Volume50
Issue number5
DOIs
StatePublished - May 1 2009
Externally publishedYes

Keywords

  • Carotid artery disease
  • Genome-wide association study
  • Kringle IV
  • LPA

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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  • Cite this

    Ober, C., Nord, A., Thompson, E. E., Pan, L., Tan, Z., Cusanovich, D., Sun, Y., Nicolae, R., Edelstein, C., Schneider, D. H., Billstrand, C., Pfaffinger, D., Phillips, N., Anderson, R. L., Philips, B., Rajagopalan, R., Hatsukami, T. S., Rieder, M. J., Heagerty, P. J., ... Nicolae, D. L. (2009). Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q. Journal of Lipid Research, 50(5), 798-806. https://doi.org/10.1194/jlr.M800515-JLR200