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Mendelian randomization of blood lipids for coronary heart disease.
Wednesday,2015-03-04 12:37 America/Los_Angeles — zdrager
| Title | Mendelian randomization of blood lipids for coronary heart disease. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Holmes, MV, Asselbergs, FW, Palmer, TM, Drenos, F, Lanktree, MB, Nelson, CP, Dale, CE, Padmanabhan, S, Finan, C, Swerdlow, DI, Tragante, V, van Iperen, EPA, Sivapalaratnam, S, Shah, S, Elbers, CC, Shah, T, Engmann, J, Giambartolomei, C, White, J, Zabaneh, D, Sofat, R, McLachlan, S, Doevendans, PA, Balmforth, AJ, Hall, AS, North, KE, Almoguera, B, Hoogeveen, RC, Cushman, M, Fornage, M, Patel, SR, Redline, S, Siscovick, DS, Tsai, MY, Karczewski, KJ, Hofker, MH, W Verschuren, M, Bots, ML, van der Schouw, YT, Melander, O, Dominiczak, AF, Morris, R, Ben-Shlomo, Y, Price, J, Kumari, M, Baumert, J, Peters, A, Thorand, B, Koenig, W, Gaunt, TR, Humphries, SE, Clarke, R, Watkins, H, Farrall, M, Wilson, JG, Rich, SS, de Bakker, PIW, Lange, LA, Smith, GDavey, Reiner, AP, Talmud, PJ, Kivimaki, M, Lawlor, DA, Dudbridge, F, Samani, NJ, Keating, BJ, Hingorani, AD, Casas, JP |
| Corporate/Institutional Authors | UCLEB consortium |
| Journal | Eur Heart J |
| Volume | 36 |
| Issue | 9 |
| Pagination | 539-50 |
| Date Published | 2015 Mar 01 |
| ISSN | 1522-9645 |
| Keywords | Case-Control Studies, Cholesterol, HDL, Coronary Artery Disease, Female, Gene Frequency, Genotype, Genotyping Techniques, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk Assessment, Triglycerides |
| Abstract | <p><b>AIMS: </b>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.</p><p><b>METHODS AND RESULTS: </b>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).</p><p><b>CONCLUSION: </b>The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.</p> |
| DOI | 10.1093/eurheartj/eht571 |
| Alternate Journal | Eur. Heart J. |
| PubMed ID | 24474739 |
| PubMed Central ID | PMC4344957 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States 090532/Z/09/Z / / Wellcome Trust / United Kingdom CZB/4/672 / / Chief Scientist Office / United Kingdom N01-HC-95162 / HC / NHLBI NIH HHS / United States RG/13/2/30098 / / British Heart Foundation / United Kingdom RG/08/008/25291 / / British Heart Foundation / United Kingdom 33014 / / PHS HHS / United States PG/13/66/30442 / / British Heart Foundation / United Kingdom N01WH42129-32 / WH / WHI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States MR/K006215/1 / / Medical Research Council / United Kingdom RG/07/005/23633 / / British Heart Foundation / United Kingdom N01-HC-55022 / HC / NHLBI NIH HHS / United States RR-024156 / RR / NCRR NIH HHS / United States N01-HC-95163 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01-HC-95168 / HC / NHLBI NIH HHS / United States N01WH32100-2 / WH / WHI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States UL1 RR024156 / RR / NCRR NIH HHS / United States MC_UU_12019/1 / / Medical Research Council / United Kingdom N01-HC-95159 / HC / NHLBI NIH HHS / United States N01WH32108-9 / WH / WHI NIH HHS / United States / / Department of Health / United Kingdom N01HC55022 / HL / NHLBI NIH HHS / United States N01-HC-95165 / HC / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01WH42107-26 / WH / WHI NIH HHS / United States HHSN268200960009C / / PHS HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States HL36310 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-95169 / HC / NHLBI NIH HHS / United States N01WH32122 / WH / WHI NIH HHS / United States N01-HC-95164 / HC / NHLBI NIH HHS / United States PG/07/131/24254 / / British Heart Foundation / United Kingdom MC_UU_12013/1 / / Medical Research Council / United Kingdom N01HC95159 / HL / NHLBI NIH HHS / United States 090532 / / Wellcome Trust / United Kingdom N01-HC-55020 / HC / NHLBI NIH HHS / United States RG 08/008 / / British Heart Foundation / United Kingdom N01-HC-95160 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States R01AG1764406S1 / AG / NIA NIH HHS / United States N01WH32105-6 / WH / WHI NIH HHS / United States N01WH32111-13 / WH / WHI NIH HHS / United States G0802432 / / Medical Research Council / United Kingdom N01WH32118-32119 / WH / WHI NIH HHS / United States CH/98001 / / British Heart Foundation / United Kingdom N01HC55019 / HL / NHLBI NIH HHS / United States R01 AG017644 / AG / NIA NIH HHS / United States MR/K006584/1 / / Medical Research Council / United Kingdom MR/K013351/1 / / Medical Research Council / United Kingdom N01-HC-95161 / HC / NHLBI NIH HHS / United States PG/07/133/24260 / / British Heart Foundation / United Kingdom N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States N01-HC-95166 / HC / NHLBI NIH HHS / United States G1000718 / / Medical Research Council / United Kingdom MC_UU_12013/5 / / Medical Research Council / United Kingdom N01WH32115 / WH / WHI NIH HHS / United States MR/L01629X/1 / / Medical Research Council / United Kingdom N01WH44221 / WH / WHI NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States MC_UU_12013/8 / / Medical Research Council / United Kingdom N01WH24152 / WH / WHI NIH HHS / United States N01-HC-95167 / HC / NHLBI NIH HHS / United States N01-HC-65226 / HC / NHLBI NIH HHS / United States RG/10/12/28456 / / British Heart Foundation / United Kingdom |