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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genetics ; Epidemiology ; Coronary Artery Disease; Coronary-artery-disease; Genetic-variants; Plasma Lipoprotein(a); Myocardial-infarction; Molecular-basis; Lpa Locus; Lp(a); Risk; Identification; Caucasians
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 0022-2275
e-ISSN 1539-7262
Zeitschrift Journal of Lipid Research
Quellenangaben Band: 58, Heft: 9, Seiten: 1834-1844 Artikelnummer: , Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Verlagsort Bethesda
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-004
G-504000-002
G-504100-001
G-501900-402
G-500700-001
G-504090-001
DOI 10.1194/jlr.M076232
WOS ID WOS:000408912600010
Scopus ID 85029424122
PubMed ID 28512139
Erfassungsdatum 2017-09-22
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