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Mack, S.* ; Coassin, S.* ; Rueedi, R.* ; Yousri, N.A.* ; Seppälä, I.* ; Gieger, C. ; Schoenherr, S.* ; Forer, L.* ; Erhart, G.* ; Marques-Vidal, P.* ; Ried, J.S. ; Waeber, G.* ; Bergmann, S.* ; Daehnhardt, D.* ; Stoeckl, A.* ; Raitakari, O.T.* ; Khahonen, M.* ; Peters, A. ; Meitinger, T. ; Strauch, K. ; Kedenko, L.* ; Paulweber, B.* ; Lehtimäki, T.J.* ; Hunt, S.C.* ; Vollenweider, P.* ; Lamina, C.* ; Kronenberg, F.*

A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

J. Lipid Res. 58, 1834-1844 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio = 1.73, P = 3.35 × 10−30). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the APOE2-determining allele of rs7412 to be significantly associated with Lp(a) concentrations (P = 3.47 × 10−10). Each APOE2 allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the population’s mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the TLR2 gene with Lp(a) (P = 3.4 × 10−4). In summary, we identified a large number of independent SNPs in the LPA gene region, as well as the APOE2 allele, to be significantly associated with Lp(a) concentrations.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genetics ; Epidemiology ; Coronary Artery Disease; Coronary-artery-disease; Genetic-variants; Plasma Lipoprotein(a); Myocardial-infarction; Molecular-basis; Lpa Locus; Lp(a); Risk; Identification; Caucasians
ISSN (print) / ISBN 0022-2275
e-ISSN 1539-7262
Journal Journal of Lipid Research
Quellenangaben Volume: 58, Issue: 9, Pages: 1834-1844 Article Number: , Supplement: ,
Publisher American Society for Biochemistry and Molecular Biology
Publishing Place Bethesda
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)