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Holmes, M.V.* ; Asselbergs, F.W.* ; Palmer, T.M.* ; Drenos, F.* ; Lanktree, M.B.* ; Nelson, C.P.* ; Dale, C.E.* ; Padmanabhan, S.* ; Finan, C.* ; Swerdlow, D.I.* ; Tragante, V.* ; van Iperen, E.P.* ; Sivapalaratnam, S.* ; Shah, S.* ; Elbers, C.C.* ; Shah, T.* ; Engmann, J.* ; Giambartolomei, C.* ; White, J.* ; Zabaneh, D.* ; Sofat, R.* ; McLachlan, S.* ; Doevendans, P.A.* ; Balmforth, A.J.* ; Hall, A.S.* ; North, K.E.* ; Almoguera, B.* ; Hoogeveen, R.C.* ; Cushman, M.* ; Fornage, M.* ; Patel, S.R.* ; Redline, S.* ; Siscovick, D.S.* ; Tsai, M.Y.* ; Karczewski, K.J.* ; Hofker, M.H.* ; Verschuren, W.M.* ; Bots, M.L.* ; van der Schouw, Y.T.* ; Melander, O.* ; Dominiczak, A.F.* ; Morris, R.W.* ; Ben-Shlomo, Y.* ; Price, J.F.* ; Kumari, M.* ; Baumert, J.J. ; Peters, A. ; Thorand, B. ; Koenig, W.* ; Gaunt, T.R.* ; Humphries, S.E.* ; Clarke, R.* ; Watkins, H.* ; Farrall, M.* ; Wilson, J.G.* ; Rich, S.S.* ; de Bakker, P.I.* ; Lange, L.A.* ; Davey Smith, G.* ; Reiner, A.P.* ; Talmud, P.J.* ; Kivimaki, M.* ; Lawlor, D.A.* ; Dudbridge, F.* ; Samani, N.J.* ; Keating, B.J.* ; Hingorani, A.D.* ; Casas, J.P.*

Mendelian randomization of blood lipids for coronary heart disease.

Eur. Heart J. 36, 539-550 (2015)
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AIMS: To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. METHODS AND RESULTS: We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10-6); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). CONCLUSION: The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.  
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Aetiology ; Epidemiology ; Heart Disease ; Lipids ; Mendelian Randomization; High-density-lipoprotein; Instrumental Variables; Genetic-variants; Cardiovascular Events; Cholesterol Levels; Vascular-disease; Risk-factors; Metaanalysis; Trials; Atherosclerosis
Sprache englisch
Veröffentlichungsjahr 2015
Prepublished im Jahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 0195-668X
e-ISSN 1522-9645
Zeitschrift European Heart Journal
Quellenangaben Band: 36, Heft: 9, Seiten: 539-550 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504000-002
G-504000-003
PubMed ID 24474739
DOI 10.1093/eurheartj/eht571
WOS ID WOS:000351591800007
Scopus ID 84924420487
Erfassungsdatum 2014-03-10
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