title: Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q.
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.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA. c-ober@genetics.uchicago.edu
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.forename: Alex S
authors.initials: AS
authors.lastname: Nord
authors.forename: Emma E
authors.initials: EE
authors.lastname: Thompson
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.forename: Darren
authors.initials: D
authors.lastname: Cusanovich
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Raluca
authors.initials: R
authors.lastname: Nicolae
authors.forename: Celina
authors.initials: C
authors.lastname: Edelstein
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Schneider
authors.forename: Christine
authors.initials: C
authors.lastname: Billstrand
authors.forename: Ditta
authors.initials: D
authors.lastname: Pfaffinger
authors.forename: Natasha
authors.initials: N
authors.lastname: Phillips
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Anderson
authors.forename: Binu
authors.initials: B
authors.lastname: Philips
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Rajagopalan
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Hatsukami
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Rieder
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Heagerty
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.forename: Mark
authors.initials: M
authors.lastname: Abney
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Scanu
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D018082:Kringles / Q000235:genetics; D015810:Linkage Disequilibrium; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012067:Religion; D013023:South Dakota; D044465:White People / Q000235:genetics
chemical_list: D017270:Lipoprotein(a); D020033:Protein Isoforms