ITEM METADATA RECORD
Title: Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study
Authors: Voight, Benjamin F ×
Peloso, Gina M
Orho-Melander, Marju
Frikke-Schmidt, Ruth
Barbalic, Maja
Jensen, Majken K
Hindy, George
Holm, Hilma
Ding, Eric L
Johnson, Toby
Schunkert, Heribert
Samani, Nilesh J
Clarke, Robert
Hopewell, Jemma C
Thompson, John F
Li, Mingyao
Thorleifsson, Gudmar
Newton-Cheh, Christopher
Musunuru, Kiran
Pirruccello, James P
Saleheen, Danish
Chen, Li
Stewart, Alexandre F. R
Schillert, Arne
Thorsteinsdottir, Unnur
Thorgeirsson, Gudmundur
Anand, Sonia
Engert, James C
Morgan, Thomas
Spertus, John
Stoll, Monika
Berger, Klaus
Martinelli, Nicola
Girelli, Domenico
McKeown, Pascal P
Patterson, Christopher C
Epstein, Stephen E
Devaney, Joseph
Burnett, Mary-Susan
Mooser, Vincent
Ripatti, Samuli
Surakka, Ida
Nieminen, Markku S
Sinisalo, Juha
Lokki, Marja-Liisa
Perola, Markus
Havulinna, Aki
de Faire, Ulf
Gigante, Bruna
Ingelsson, Erik
Zeller, Tanja
Wild, Philipp
de Bakker, Paul I W
Klungel, Olaf H
Maitland-van der Zee, Anke-Hilse
Peters, Bas J M
de Boer, Anthonius
Grobbee, Diederick E
Kamphuisen, Pieter W
Deneer, Vera H M
Elbers, Clara C
Onland-Moret, N Charlotte
Hofker, Marten H
Wijmenga, Cisca
Verschuren, Wm Monique
Boer, Jolanda Ma
van der Schouw, Yvonne T
Rasheed, Asif
Frossard, Philippe
Demissie, Serkalem
Willer, Cristen
Doll, Ronald
Ordovas, Jose M
Abecasis, Goncalo R
Boehnke, Michael
Mohlke, Karen L
Daly, Mark J
Guiducci, Candace
Burtt, Noel P
Surti, Aarti
Gonzalez, Elena
Purcell, Shaun
Gabriel, Stacey
Marrugat, Jaume
Peden, John
Erdmann, Jeanette
Diemert, Patrick
Willenborg, Christina
Koenig, Inke R
Fischer, Marcus
Hengstenberg, Christian
Ziegler, Andreas
Buysschaert, Ian
Lambrechts, Diether
Van de Werf, Frans
Fox, Keith A
El Mokhtari, Nour Eddine
Rubin, Diana
Schrezenmeir, Juergen
Schreiber, Stefan
Schaefer, Arne
Danesh, John
Blankenberg, Stefan
Roberts, Robert
McPherson, Ruth
Watkins, Hugh
Hall, Alistair S
Overvad, Kim
Rimm, Eric
Boerwinkle, Eric
Tybjaerg-Hansen, Anne
Cupples, L Adrienne
Reilly, Muredach P
Melander, Olle
Mannucci, Pier M
Ardissino, Diego
Siscovick, David
Elosua, Roberto
Stefansson, Kari
O'Donnell, Christopher J
Salomaa, Veikko
Rader, Daniel J
Peltonen, Leena
Schwartz, Stephen M
Altshuler, David
Kathiresan, Sekar #
Issue Date: May-2012
Publisher: The Lancet Publishing Group
Series Title: The Lancet vol:380 issue:9841 pages:572-580
Abstract: BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol. FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)). INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction. FUNDING: US National Institutes of Health, The Wellcome Trust, European Union, British Heart Foundation, and the German Federal Ministry of Education and Research.
URI: 
ISSN: 0140-6736
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
Cardiology
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science