title: Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study.
abstract: Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease. Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart Study. We observed that local ancestry at 6q25.3 was an important risk factor for Lp(a) in AAs, and that multiple single-nucleotide polymorphisms (SNPs) at the well-established LPA locus were significantly associated with Lp(a) (P<5 × 10(-8)) after adjusting for the local ancestry at 6q25.3. Interestingly, before adjusting for local ancestry, we observed significant (P<5 × 10(-8)) associations for hundreds of SNPs spanning ~10 Mb region on 6q surrounding the LPA gene, whereas after adjusting for local ancestry, the region containing significantly associated SNPs got much narrower and was centered over the LPA gene (<1 Mb). We observed a single nonsynonymous SNP in APOE significantly associated with Lp(a) (P<5 × 10(-8)). A high burden of coding variants in LPA and APOE were also associated with higher Lp(a) levels. Our study provides evidence that ancestry-specific causal risk variant(s) resides in or near LPA and that most of the observed associations outside this narrower region are spurious associations.
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sabourin
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: William
authors.initials: W
authors.lastname: Valdar
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Monte S
authors.initials: MS
authors.lastname: Willis
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
mesh_terms: D001741:Black or African American; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D017270:Lipoprotein(a) / Q000235:genetics*; D008297:Male; D008922:Mississippi; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D001057:Apolipoproteins E; D017270:Lipoprotein(a)