Research Repository

Mendelian randomization of blood lipids for coronary heart disease

Holmes, MV and Asselbergs, FW and Palmer, TM and Drenos, F and Lanktree, MB and Nelson, CP and Dale, CE and Padmanabhan, S and Finan, C and Swerdlow, DI and Tragante, V and Van Iperen, EPA and Sivapalaratnam, S and Shah, S and Elbers, CC and Shah, T and Engmann, J and Giambartolomei, C and White, J and Zabaneh, D and Sofat, R and McLachlan, S and Doevendans, PA and Balmforth, AJ and Hall, AS and North, KE and Almoguera, B and Hoogeveen, RC and Cushman, M and Fornage, M and Patel, SR and Redline, S and Siscovick, DS and Tsai, MY and Karczewski, KJ and Hofker, MH and Verschuren, WM and Bots, ML and Van Der Schouw, YT and Melander, O and Dominiczak, AF and Morris, R and Ben-Shlomo, Y and Price, J and Kumari, M and Baumert, J and Peters, A and Thorand, B and Koenig, W and Gaunt, TR and Humphries, SE and Clarke, R and Watkins, H and Farrall, M and Wilson, JG and Rich, SS and De Bakker, PIW and Lange, LA and Smith, GD and Reiner, AP and Talmud, PJ and Kivimäki, M and Lawlor, DA and Dudbridge, F and Samani, NJ and Keating, BJ and Hingorani, AD and Casas, JP (2015) 'Mendelian randomization of blood lipids for coronary heart disease.' European Heart Journal, 36 (9). 539 - 550. ISSN 0195-668X

[img]
Preview
Text
539.full.pdf - Published Version

Download (697kB) | Preview

Abstract

© The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology. 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.

Item Type: Article
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 28 Sep 2015 11:22
Last Modified: 15 Nov 2017 01:15
URI: http://repository.essex.ac.uk/id/eprint/15074

Actions (login required)

View Item View Item