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Mendelian randomization of blood lipids for coronary heart disease.

TitleMendelian randomization of blood lipids for coronary heart disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsHolmes 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
Secondary AuthorsCasas JP
Corporate AuthorsUCLEB consortium
JournalEur Heart J
Volume36
Issue9
Pagination539-50
Date Published2015 Mar 01
ISSN1522-9645
KeywordsCase-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

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

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.
DOI10.1093/eurheartj/eht571
Alternate JournalEur Heart J
PubMed ID24474739
PubMed Central IDPMC4344957
Grant ListN01HC55020 / 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
/ / Wellcome Trust / United Kingdom
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