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Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

TitleAssociation between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
Publication TypeJournal Article
Year of Publication2014
AuthorsHolmes MV, Dale CE, Zuccolo L, et al.
Secondary AuthorsCasas JP
Corporate AuthorsInterAct Consortium
JournalBMJ
Volume349
Paginationg4164
Date Published2014 Jul 10
ISSN1756-1833
KeywordsAdult, Aged, Alcohol Dehydrogenase, Alcohol Drinking, Biomarkers, Coronary Disease, Female, Genetic Markers, Genotype, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Models, Statistical, Polymorphism, Single Nucleotide, Stroke
Abstract

OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.

DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies.

PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.

MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.

RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).

CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

DOI10.1136/bmj.g4164
Alternate JournalBMJ
PubMed ID25011450
PubMed Central IDPMC4091648
Grant List090532/Z/09/Z / / Wellcome Trust / United Kingdom
HL34594 / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
AA021223-01 / AA / NIAAA NIH HHS / United States
AA11181 / AA / NIAAA NIH HHS / United States
G1001799 / / Medical Research Council / United Kingdom
RG/08/013/25942 / / British Heart Foundation / United Kingdom
WT087997MA / / Wellcome Trust / United Kingdom
HHSN268200900009C / / PHS HHS / United States
092731 / / Wellcome Trust / United Kingdom
RG/08/008/25291 / / British Heart Foundation / United Kingdom
PG/13/66/30442 / / British Heart Foundation / United Kingdom
078557 / / Wellcome Trust / United Kingdom
R01HL59367 / HL / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
G19/35 / / Medical Research Council / United Kingdom
RG/07/005/23633 / / British Heart Foundation / United Kingdom
0090049 / / Department of Health / United Kingdom
HHSN271201100004C / / PHS HHS / United States
G1000718 / / Medical Research Council / United Kingdom
N01-HC-48047 / HC / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
MC_UU_12019/1 / / Medical Research Council / United Kingdom
P30 CA015704 / CA / NCI NIH HHS / United States
HHSN268201100001C / / PHS HHS / United States
G0100222 / / Medical Research Council / United Kingdom
HHSN268201100005C / / PHS HHS / United States
AG1764406S1 / AG / NIA NIH HHS / United States
PG/2008/008 / / British Heart Foundation / United Kingdom
HL 114901 / HL / NHLBI NIH HHS / United States
G0600580 / / Medical Research Council / United Kingdom
HHSN268201100009C / / PHS HHS / United States
AG13196 / AG / NIA NIH HHS / United States
CA87969 / CA / NCI NIH HHS / United States
G8802774 / / Medical Research Council / United Kingdom
G1000143 / / Medical Research Council / United Kingdom
G0902037 / / Medical Research Council / United Kingdom
N01-HC-95095 / HC / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
CA55075 / CA / NCI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MC_UU_12013/1 / / Medical Research Council / United Kingdom
HHSN268201100010C / / PHS HHS / United States
102215 / / Wellcome Trust / United Kingdom
HHSN268200960009C / / PHS HHS / United States
MC_UU_12015/1 / / Medical Research Council / United Kingdom
N01-HC-48050 / HC / NHLBI NIH HHS / United States
PG/09/022 / / British Heart Foundation / United Kingdom
076113 / / Wellcome Trust / United Kingdom
U01HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100003C / / PHS HHS / United States
MC_U106179471 / / Medical Research Council / United Kingdom
HHSN268201100004C / / PHS HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
064947/Z/01/Z / / Wellcome Trust / United Kingdom
MC_PC_15018 / / Medical Research Council / United Kingdom
HHSN268201100008C / / PHS HHS / United States
P20 MD006899 / MD / NIMHD NIH HHS / United States
14136 / / Cancer Research UK / United Kingdom
P20MD006899 / MD / NIMHD NIH HHS / United States
HL36310 / HL / NHLBI NIH HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01 HL114901 / HL / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HL46380 / HL / NHLBI NIH HHS / United States
G1000616 / / Medical Research Council / United Kingdom
G0401527 / / Medical Research Council / United Kingdom
PG/07/131/24254 / / British Heart Foundation / United Kingdom
G0701863 / / Medical Research Council / United Kingdom
N01-HC-48049 / HC / NHLBI NIH HHS / United States
G0701830 / / Medical Research Council / United Kingdom
090532 / / Wellcome Trust / United Kingdom
N01HC85086 / HC / NHLBI NIH HHS / United States
RG2008/014 / / British Heart Foundation / United Kingdom
G0902144 / / Medical Research Council / United Kingdom
N01HC85082 / HC / NHLBI NIH HHS / United States
HL35464 / HL / NHLBI NIH HHS / United States
F32DA024920 / DA / NIDA NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
RG/10/12/28456 / / British Heart Foundation / United Kingdom
R21 AA021223 / AA / NIAAA NIH HHS / United States
G0802432 / / Medical Research Council / United Kingdom
CH/98001 / / British Heart Foundation / United Kingdom
HHSN268200800007C / / PHS HHS / United States
MR/K006584/1 / / Medical Research Council / United Kingdom
MR/K013351/1 / / Medical Research Council / United Kingdom
HHSN268201100011C / / PHS HHS / United States
HHSN268201100046C / / PHS HHS / United States
R01 42733 / / PHS HHS / United States
HHSN268201200036C / / PHS HHS / United States
1R01 AG23522 / AG / NIA NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
RG/13/16/30528 / / British Heart Foundation / United Kingdom
WT088806 / / Wellcome Trust / United Kingdom
N01-HC-48048 / HC / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
NIH HL075451 / HL / NHLBI NIH HHS / United States
MRC G0601653 / / Medical Research Council / United Kingdom
HHSN268201100002C / / PHS HHS / United States
AG023629 / AG / NIA NIH HHS / United States
MC_UU_12013/5 / / Medical Research Council / United Kingdom
G0000934 / / Medical Research Council / United Kingdom
RG/98002 / / British Heart Foundation / United Kingdom
N01HC65226 / HC / NHLBI NIH HHS / United States
G0601647 / / Medical Research Council / United Kingdom
R01 NS39987 / NS / NINDS NIH HHS / United States
MC_UU_12013/8 / / Medical Research Council / United Kingdom
U01 DK062418 / DK / NIDDK NIH HHS / United States
NHLBI 33014 / / PHS HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
N01 HC55222 / HC / NHLBI NIH HHS / United States
081081/Z/06/Z / / Wellcome Trust / United Kingdom
RG/07/008/23674 / / British Heart Foundation / United Kingdom