Genetics
A genome-wide study finds at least 6 genes beyond LPA that independently affect Lp(a) levels, a study of 386 people (J Lipid Res 2009)
Original title: Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q
This genome-wide association study examined plasma Lp(a) in 386 members of a communal-living founder population, identifying 77 SNPs spanning 12.5 Mb on chromosome 6q26-q27 that reached genome-wide significance (P<=1.3x10-7), located within or near nine genes including LPA. Variation in at least six genes beyond LPA was independently associated with Lp(a) levels, separate from each other and from the LPA kringle IV repeat polymorphism. A novel SNP in LPA intron 37 was also associated with Lp(a) levels and carotid artery disease count in unrelated Caucasians (P=7.3x10-12 and 0.024, respectively), independent of kringle IV number. The findings suggest a complex genetic architecture for Lp(a), involving multiple loci across chromosome 6q26-q27 beyond the LPA gene itself.
Original 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.