The associations of plasma phospholipid arachidonic acid with cardiovascular diseases: A Mendelian randomization study

被引:39
作者
Zhang, Ting [1 ]
Zhao, Jie, V [1 ]
Schooling, C. Mary [1 ,2 ]
机构
[1] Univ Hong Kong, Li Ka Shing Fac Med, Sch Publ Hlth, Hong Kong, Peoples R China
[2] CUNY, Sch Publ Hlth & Hlth Policy, New York, NY 10021 USA
关键词
Arachidonic acid; Atherosclerotic cardiovascular disease; Mendelian randomization; GENOME-WIDE ASSOCIATION; FATTY-ACIDS; MYOCARDIAL-INFARCTION; HEART; RISK; DIETARY; POLYMORPHISMS; TESTOSTERONE; EPIDEMIOLOGY; METAANALYSIS;
D O I
10.1016/j.ebiom.2020.103189
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Arachidonic acid (AA), a major long-chain n-6 polyunsaturated fatty acid in animal foods, has been linked to inflammation, coagulation, and testosterone, which might relate to atherosclerotic cardiovascular diseases (ASCVD). We assessed the associations of genetically predicted plasma phospholipid AA with ASCVD and other CVD overall and by sex using Mendelian randomization (MR). Methods: We conducted two-sample MR, applying eight genetic variants, independent of a highly pleiotropic variant (rs174547), strongly (p < 5 x 10(-8)) predicting AA, primarily to summary statistics of genetic associations with ASCVD, including ischaemic heart disease (IHD), ischaemic stroke, and peripheral artery disease (PAD) from CARDIoGRAMplusC4D 1000 Genomes (60,801 IHD cases, 123,504 controls), MEGASTROKE (34,217 ischaemic stroke cases, 406,111 controls), and Pan-UK Biobank (n=similar to 420,531), and secondarily to genetic associations with other CVD from Pan-UK Biobank, Atrial Fibrillation Consortium, HERMES consortium, and FinnGen. We also assessed sex differences. Findings: Genetically predicted AA was associated with ASCVD (odds ratio (OR) per % of total fatty acids increase 1.03, 95% confidence interval (CI) 1.01 to 1.05) and its subtypes IHD (OR 1.03, 95% CI 1.004 to 1.05), ischaemic stroke (OR 1.03, 95% CI 1.004 to 1.06) and possibly PAD (OR 1.08, 95% CI 1.00 to 1.17), possibly more strongly in men than women. AA was also associated with venous thromboembolism (OR 1.12, 95% CI 1.05 to 1.19). A similar pattern was observed when using rs174547 to genetically predict AA. Interpretation: Our study suggests positive associations of AA with ASCVD and venous thromboembolism, with possibly stronger associations in men than women. (C) 2020 The Authors. Published by Elsevier B.V.
引用
收藏
页数:7
相关论文
共 52 条
[1]  
[Anonymous], 1977, US SEN SEL COMM NUTR, V1st
[2]  
[Anonymous], 1980, 7 COUNTRIES MULTIVAR
[3]  
[Anonymous], 2015 2020 DIET GUID
[4]   Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia [J].
Bhatt, Deepak L. ;
Steg, P. Gabriel ;
Miller, Michael ;
Brinton, Eliot A. ;
Jacobson, Terry A. ;
Ketchum, Steven B. ;
Doyle, Ralph T., Jr. ;
Juliano, Rebecca A. ;
Jiao, Lixia ;
Granowitz, Craig ;
Tardif, Jean-Claude ;
Ballantyne, Christie M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (01) :11-22
[5]   Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I2 statistic [J].
Bowden, Jack ;
Del Greco, Fabiola M. ;
Minelli, Cosetta ;
Smith, George Davey ;
Sheehan, Nuala A. ;
Thompson, John R. .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2016, 45 (06) :1961-1974
[6]   Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator [J].
Bowden, Jack ;
Smith, George Davey ;
Haycock, Philip C. ;
Burgess, Stephen .
GENETIC EPIDEMIOLOGY, 2016, 40 (04) :304-314
[7]   Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data [J].
Burgess, Stephen ;
Butterworth, Adam ;
Thompson, Simon G. .
GENETIC EPIDEMIOLOGY, 2013, 37 (07) :658-665
[8]   The UK Biobank resource with deep phenotyping and genomic data [J].
Bycroft, Clare ;
Freeman, Colin ;
Petkova, Desislava ;
Band, Gavin ;
Elliott, Lloyd T. ;
Sharp, Kevin ;
Motyer, Allan ;
Vukcevic, Damjan ;
Delaneau, Olivier ;
O'Connell, Jared ;
Cortes, Adrian ;
Welsh, Samantha ;
Young, Alan ;
Effingham, Mark ;
McVean, Gil ;
Leslie, Stephen ;
Allen, Naomi ;
Donnelly, Peter ;
Marchini, Jonathan .
NATURE, 2018, 562 (7726) :203-+
[9]   A systematic review of the effects of increasing arachidonic acid intake on PUFA status, metabolism and health-related outcomes in humans [J].
Calder, Philip C. ;
Campoy, Cristina ;
Eilander, Ans ;
Fleith, Mathilde ;
Forsyth, Stewart ;
Larsson, Per-Olof ;
Schelkle, Bettina ;
Lohner, Szimonetta ;
Szommer, Aliz ;
van de Heijning, Bert J. M. ;
Mensink, Ronald P. .
BRITISH JOURNAL OF NUTRITION, 2019, 121 (11) :1201-1214
[10]   Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk A Systematic Review and Meta-analysis [J].
Chowdhury, Rajiv ;
Warnakula, Samantha ;
Kunutsor, Setor ;
Crowe, Francesca ;
Ward, Heather A. ;
Johnson, Laura ;
Franco, Oscar H. ;
Butterworth, Adam S. ;
Forouhi, Nita G. ;
Thompson, Simon G. ;
Khaw, Kay-Tee ;
Mozaffarian, Dariush ;
Danesh, John ;
Di Angelantonio, Emanuele .
ANNALS OF INTERNAL MEDICINE, 2014, 160 (06) :398-+