title: Alcohol intake and cardiovascular risk factors: A Mendelian randomisation study.
abstract: Mendelian randomisation studies from Asia suggest detrimental influences of alcohol on cardiovascular risk factors, but such associations are observed mainly in men. The absence of associations of genetic variants (e.g. rs671 in ALDH2) with such risk factors in women - who drank little in these populations - provides evidence that the observations are not due to genetic pleiotropy. Here, we present a Mendelian randomisation study in a South Korean population (3,365 men and 3,787 women) that 1) provides robust evidence that alcohol consumption adversely affects several cardiovascular disease risk factors, including blood pressure, waist to hip ratio, fasting blood glucose and triglyceride levels. Alcohol also increases HDL cholesterol and lowers LDL cholesterol. Our study also 2) replicates sex differences in associations which suggests pleiotropy does not underlie the associations, 3) provides further evidence that association is not due to pleiotropy by showing null effects in male non-drinkers, and 4) illustrates a way to measure population-level association where alcohol intake is stratified by sex. In conclusion, population-level instrumental variable estimation (utilizing interaction of rs671 in ALDH2 and sex as an instrument) strengthens causal inference regarding the largely adverse influence of alcohol intake on cardiovascular health in an Asian population.
authors.affiliation: Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul, Republic of Korea.
authors.forename: Yoonsu
authors.initials: Y
authors.lastname: Cho
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social &Community Medicine, University of Bristol, Bristol, UK.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Public Health Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sungho
authors.initials: S
authors.lastname: Won
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social &Community Medicine, University of Bristol, Bristol, UK.|Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social &Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Department of Public Health Sciences, BK21PLUS Program in Embodiment: Health-Society Interaction, Graduate School, Korea University, Seoul, Republic of Korea.|Korea University Guro Hospital, Korea University, Seoul, Republic of Korea.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Shin
mesh_terms: D000428:Alcohol Drinking / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D049629:Waist-Hip Ratio
chemical_list: D001786:Blood Glucose; D014280:Triglycerides; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial