Journal
JOURNAL OF LIPID RESEARCH
Volume 50, Issue 5, Pages 798-806Publisher
ELSEVIER
DOI: 10.1194/jlr.M800515-JLR200
Keywords
genome-wide association study; LPA; carotid artery disease; kringle IV
Categories
Funding
- National Institutes of Health [R01 HL66533, R01 HL63209, P50 HL56399, M01 RR00055, U01 HL66682, R01 HL074366, R01HL67406, P01 HL30086, P01 HL072262]
- Hoffman-LaRoche to the University of Chicago
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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 x 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 x 10(-12) and 0.024, respectively), also independent of kringle IV number. jlr This study suggests a complex genetic architecture of Lp(a) levels that may involve multiple loci on chromosome 6q26-q27.-Ober, C., A. S. Nord, E. E. Thompson, L. Pan, Z. Tan, D. Cusanovich, Y. Sun, R. Nicolae, C. Edelstein, D. H. Schneider, C. Billstrand, D. Pfaffinger, N. Phillips, R. L. Anderson, B. Philips, R. Rajagopalan, T. S. Hatsukami, M. J. Rieder, P. J. Heagerty, D. A. Nickerson, M. Abney, S. Marcovina, G. P. Jarvik, A. M. Scanu, and D. L. Nicolae. Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q. J. Lipid Res. 2009. 50: 798-806.
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