Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Association between alcohol and cardiovascular disease
T2 - Mendelian randomisation analysis based on individual participant data
AU - Holmes, Michael V
AU - Dale, Caroline E
AU - Zuccolo, Luisa
AU - Silverwood, Richard J
AU - Guo, Yiran
AU - Ye, Zheng
AU - Prieto-Merino, David
AU - Dehghan, Abbas
AU - Trompet, Stella
AU - Wong, Andrew
AU - Cavadino, Alana
AU - Drogan, Dagmar
AU - Padmanabhan, Sandosh
AU - Li, Shanshan
AU - Yesupriya, Ajay
AU - Leusink, Maarten
AU - Sundstrom, Johan
AU - Hubacek, Jaroslav A
AU - Pikhart, Hynek
AU - Swerdlow, Daniel I
AU - Panayiotou, Andrie G
AU - Borinskaya, Svetlana A
AU - Finan, Chris
AU - Shah, Sonia
AU - Kuchenbaecker, Karoline B
AU - Shah, Tina
AU - Engmann, Jorgen
AU - Folkersen, Lasse
AU - Eriksson, Per
AU - Ricceri, Fulvio
AU - Melander, Olle
AU - Sacerdote, Carlotta
AU - Gamble, Dale M
AU - Rayaprolu, Sruti
AU - Ross, Owen A
AU - McLachlan, Stela
AU - Vikhireva, Olga
AU - Sluijs, Ivonne
AU - Scott, Robert A
AU - Adamkova, Vera
AU - Flicker, Leon
AU - Bockxmeer, Frank M van
AU - Power, Christine
AU - Marques-Vidal, Pedro
AU - Meade, Tom
AU - Marmot, Michael G
AU - Ferro, Jose M
AU - Paulos-Pinheiro, Sofia
AU - Humphries, Steve E
AU - Palmer, Tom M.
AU - InterAct Consortium
N1 - © Holmes et al 2014.
PY - 2014/7/10
Y1 - 2014/7/10
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Alcohol Dehydrogenase
KW - Alcohol Drinking
KW - Biological Markers
KW - Coronary Disease
KW - Female
KW - Genetic Markers
KW - Genotype
KW - Humans
KW - Male
KW - Mendelian Randomization Analysis
KW - Middle Aged
KW - Models, Statistical
KW - Polymorphism, Single Nucleotide
KW - Stroke
U2 - 10.1136/bmj.g4164
DO - 10.1136/bmj.g4164
M3 - Journal article
C2 - 25011450
VL - 349
JO - BMJ
JF - BMJ
SN - 0959-8138
M1 - g4164
ER -