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PMID: 19124843 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Journal of lipid research ·Vol. 50 ·No. 5 ·2009-05-00 ·Pages 798-806

Ober C, Nord AS, Thompson EE, Pan L, Tan Z, Cusanovich D, Sun Y, Nicolae R, Edelstein C, Schneider DH, Billstrand C, Pfaffinger D, Phillips N, Anderson RL, Philips B, Rajagopalan R, Hatsukami TS, Rieder MJ, Heagerty PJ, Nickerson DA, Abney M, Marcovina S, Jarvik GP, Scanu AM, Nicolae DL

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 <or= 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. This study suggests a complex genetic architecture of Lp(a) levels that may involve multiple loci on chromosome 6q26-q27.

MeSH Terms
Animals Chromosome Mapping Chromosomes, Human, Pair 6/genetics Enhancer Elements, Genetic Genetic Predisposition to Disease Genome-Wide Association Study Genotype Humans Kringles/genetics Linkage Disequilibrium Lipoprotein(a)/blood,genetics Polymorphism, Single Nucleotide Protein Isoforms/blood,genetics Religion South Dakota Whites/genetics
Chemicals
Lipoprotein(a) Protein Isoforms
Authors & Affiliations
25 authors, click to expand affiliations / ORCID
Ober Carole
Department of Human Genetics, University of Chicago, Chicago, IL, USA. [email protected]
Nord Alex S
Thompson Emma E
Pan Lin
Tan Zheng
Cusanovich Darren
Sun Ying
Nicolae Raluca
Edelstein Celina
Schneider Daniel H
Billstrand Christine
Pfaffinger Ditta
Phillips Natasha
Anderson Rebecca L
Philips Binu
Rajagopalan Ramakrishnan
Hatsukami Thomas S
Rieder Mark J
Heagerty Patrick J
Nickerson Deborah A
Abney Mark
Marcovina Santica
Jarvik Gail P
Scanu Angelo M
Nicolae Dan L
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Article Info
Journal
Journal of lipid research
Abbr.
J Lipid Res
ISSN
0022-2275
DOI
10.1194/jlr.M800515-JLR200
Email
[email protected]
Published
2009-05-00
Epub
2009-00-05
Pages
798-806
Language
English
Region
United States
NLM ID
0376606
PMCID
PMC2666166
Subset
IM
Grants
NHLBI NIH HHS · R01 HL63209 · United States
NHLBI NIH HHS · R01 HL66533 · United States
NHLBI NIH HHS · R01 HL074366 · United States
NHLBI NIH HHS · P50 HL56399 · United States
NICHD NIH HHS · R01 HD021244 · United States
NCRR NIH HHS · M01 RR00055 · United States
NHLBI NIH HHS · P01 HL30086 · United States
NHLBI NIH HHS · P01 HL072262 · United States
NHLBI NIH HHS · R01 HL085197 · United States
NHLBI NIH HHS · R01HL67406 · United States
NHLBI NIH HHS · U01 HL66682 · United States
External Links
PubMed source DOI: 10.1194/jlr.M800515-JLR200 PMC Full Text View journal details
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