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

Michael V Holmes; Caroline E Dale; Luisa Zuccolo; Richard J Silverwood; Yiran Guo; Zheng Ye; David Prieto-Merino; Abbas Dehghan; Stella Trompet; Andrew Wong; Alana Cavadino; Dagmar Drogan; Sandosh Padmanabhan; Shanshan Li; Ajay Yesupriya; Maarten Leusink; Johan Sundstrom; Jaroslav A Hubacek; Hynek Pikhart; Daniel I Swerdlow; Andrie G Panayiotou; Svetlana A Borinskaya; Chris Finan; Sonia Shah; Karoline B Kuchenbaecker; Tina Shah; Jorgen Engmann; Lasse Folkersen; Per Eriksson; Fulvio Ricceri; Olle Melander; Carlotta Sacerdote; Dale M Gamble; Sruti Rayaprolu; Owen A Ross; Stela McLachlan; Olga Vikhireva; Ivonne Sluijs; Robert A Scott; Vera Adamkova; Leon Flicker; Frank M van Bockxmeer; Christine Power; Pedro Marques-Vidal; Tom Meade; Michael G Marmot; Jose M Ferro; Sofia Paulos-Pinheiro; Allan Linneberg; Børge G Nordestgaard; InterAct Consortium

doi:10.1136/bmj.g4164

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

Michael V Holmes, Caroline E Dale, Luisa Zuccolo, Richard J Silverwood, Yiran Guo, Zheng Ye, David Prieto-Merino, Abbas Dehghan, Stella Trompet, Andrew Wong, Alana Cavadino, Dagmar Drogan, Sandosh Padmanabhan, Shanshan Li, Ajay Yesupriya, Maarten Leusink, Johan Sundstrom, Jaroslav A Hubacek, Hynek Pikhart, Daniel I SwerdlowAndrie G Panayiotou, Svetlana A Borinskaya, Chris Finan, Sonia Shah, Karoline B Kuchenbaecker, Tina Shah, Jorgen Engmann, Lasse Folkersen, Per Eriksson, Fulvio Ricceri, Olle Melander, Carlotta Sacerdote, Dale M Gamble, Sruti Rayaprolu, Owen A Ross, Stela McLachlan, Olga Vikhireva, Ivonne Sluijs, Robert A Scott, Vera Adamkova, Leon Flicker, Frank M van Bockxmeer, Christine Power, Pedro Marques-Vidal, Tom Meade, Michael G Marmot, Jose M Ferro, Sofia Paulos-Pinheiro, Allan Linneberg, Børge G Nordestgaard, InterAct Consortium

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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.

Original language	English
Article number	g4164
Journal	B M J (Online)
Volume	349
Pages (from-to)	1-16
Number of pages	16
ISSN	1756-1833
DOIs	https://doi.org/10.1136/bmj.g4164
Publication status	Published - 10 Jul 2014

Keywords

Adult
Aged
Alcohol Dehydrogenase
Alcohol Drinking
Biological Markers
Coronary Disease
Female
Genetic Markers
Genotype
Humans
Male
Mendelian Randomization Analysis
Middle Aged
Models, Statistical
Polymorphism, Single Nucleotide
Stroke

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Holmes, M. V., Dale, C. E., Zuccolo, L., Silverwood, R. J., Guo, Y., Ye, Z., Prieto-Merino, D., Dehghan, A., Trompet, S., Wong, A., Cavadino, A., Drogan, D., Padmanabhan, S., Li, S., Yesupriya, A., Leusink, M., Sundstrom, J., Hubacek, J. A., Pikhart, H., ... InterAct Consortium (2014). Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. B M J (Online), 349, 1-16. Article g4164. https://doi.org/10.1136/bmj.g4164

Holmes, MV, Dale, CE, Zuccolo, L, Silverwood, RJ, Guo, Y, Ye, Z, Prieto-Merino, D, Dehghan, A, Trompet, S, Wong, A, Cavadino, A, Drogan, D, Padmanabhan, S, Li, S, Yesupriya, A, Leusink, M, Sundstrom, J, Hubacek, JA, Pikhart, H, Swerdlow, DI, Panayiotou, AG, Borinskaya, SA, Finan, C, Shah, S, Kuchenbaecker, KB, Shah, T, Engmann, J, Folkersen, L, Eriksson, P, Ricceri, F, Melander, O, Sacerdote, C, Gamble, DM, Rayaprolu, S, Ross, OA, McLachlan, S, Vikhireva, O, Sluijs, I, Scott, RA, Adamkova, V, Flicker, L, Bockxmeer, FMV, Power, C, Marques-Vidal, P, Meade, T, Marmot, MG, Ferro, JM, Paulos-Pinheiro, S, Linneberg, A , Nordestgaard, BG & InterAct Consortium 2014, 'Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data', B M J (Online), vol. 349, g4164, pp. 1-16. https://doi.org/10.1136/bmj.g4164

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title = "Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data",

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.",

keywords = "Adult, Aged, Alcohol Dehydrogenase, Alcohol Drinking, Biological Markers, Coronary Disease, Female, Genetic Markers, Genotype, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Models, Statistical, Polymorphism, Single Nucleotide, Stroke",

author = "Holmes, {Michael V} and Dale, {Caroline E} and Luisa Zuccolo and Silverwood, {Richard J} and Yiran Guo and Zheng Ye and David Prieto-Merino and Abbas Dehghan and Stella Trompet and Andrew Wong and Alana Cavadino and Dagmar Drogan and Sandosh Padmanabhan and Shanshan Li and Ajay Yesupriya and Maarten Leusink and Johan Sundstrom and Hubacek, {Jaroslav A} and Hynek Pikhart and Swerdlow, {Daniel I} and Panayiotou, {Andrie G} and Borinskaya, {Svetlana A} and Chris Finan and Sonia Shah and Kuchenbaecker, {Karoline B} and Tina Shah and Jorgen Engmann and Lasse Folkersen and Per Eriksson and Fulvio Ricceri and Olle Melander and Carlotta Sacerdote and Gamble, {Dale M} and Sruti Rayaprolu and Ross, {Owen A} and Stela McLachlan and Olga Vikhireva and Ivonne Sluijs and Scott, {Robert A} and Vera Adamkova and Leon Flicker and Bockxmeer, {Frank M van} and Christine Power and Pedro Marques-Vidal and Tom Meade and Marmot, {Michael G} and Ferro, {Jose M} and Sofia Paulos-Pinheiro and Allan Linneberg and Nordestgaard, {B{\o}rge G} and {InterAct Consortium}",

note = "{\textcopyright} Holmes et al 2014.",

year = "2014",

month = jul,

day = "10",

doi = "10.1136/bmj.g4164",

language = "English",

volume = "349",

pages = "1--16",

journal = "B M J (Online)",

issn = "1756-1833",

publisher = "B M J Group",

}

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 - Linneberg, Allan

AU - Nordestgaard, Børge G

AU - InterAct Consortium

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

SN - 1756-1833

VL - 349

SP - 1

EP - 16

JO - B M J (Online)

JF - B M J (Online)

M1 - g4164

ER -

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

Abstract

Keywords

UN SDGs

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