Search resultsIs aldehyde dehydrogenase 2 a credible genetic instrument for alcohol use in mendelian randomization analysis in southern Chinese men?
Title
Is aldehyde dehydrogenase 2 a credible genetic instrument for alcohol use in mendelian randomization analysis in southern Chinese men?
Publication type
Journal Article
Year of Publication
2013
Authors
Journal
International Journal of Epidemiology
Volume
42
Issue
1
Pagination
318 - 328
Date published
2013
ISBN
03005771 (ISSN)
Keywords
Adult, Aged, Aged, 80 and over, alanine aminotransferase, alcohol, alcohol consumption, Alcohol Drinking, aldehyde, Aldehyde Dehydrogenase, Aldehyde dehydrogenase 2, aldehyde dehydrogenase isoenzyme 2, Analysis of Variance, antidiabetic agent, antihypertensive agent, article, Asian Continental Ancestry Group, blood, body mass, cardiovascular disease, cardiovascular risk, China, Chinese men, cognition, Cohort Studies, diastolic blood pressure, economic aspect, enzyme activity, gene frequency, genetic analysis, genetic association, Genetic Predisposition to Disease, genotype, glucose, glucose blood level, health risk, high density lipoprotein cholesterol, human, Humans, Linear Models, liver function, low density lipoprotein cholesterol, major clinical study, male, Mendelian randomization, Mendelian randomization analysis, Middle Aged, mini mental state examination, physical activity, Polymorphism, Polymorphism, Single Nucleotide, Predictive Value of Tests, priority journal, risk factor, scoring system, self report, sensitivity and specificity, single nucleotide polymorphism, smoking, social aspect, socioeconomic conditions, Socioeconomic Factors, systolic blood pressure, triacylglycerol, triacylglycerol blood level
Abstract
Background Mendelian randomization studies provide a means of assessing causal relations without interventions, but require valid genetic instruments. We assessed the credibility of aldehyde dehydrogenase 2 (ALDH2) as a genetic instrument for alcohol use in Southern Chinese men. Methods We genotyped the single nucleotide polymorphism rs671 of ALDH2 in 4867 men from the Guangzhou Biobank Cohort Study. We used linear regression to assess the strength of the association of ALDH2 variants with alcohol use, whether ALDH2 variants were independently associated with socio-economic position or other potential confounders and whether associations of ALDH2 variants with cardiovascular risk factors (systolic and diastolic blood pressure, HDLand LDL-cholesterol, fasting glucose), triglycerides, body mass index, self reported cardiovascular disease, self-reported ischaemic heart disease, cognitive function (delayed 10-word recall and Mini Mental State Examination score) and liver function (alanine transaminase and aspartate transaminase) were fully mediated by alcohol use. Results The minor allele frequency (A) of ALDH2 was 0.29. The F statistic for ALDH2 variants was 75.0, suggesting that substantial weak instrument bias is unlikely. ALDH2 variants were not associated with socio-economic position, smoking or physical activity. ALDH2 variants were only associated with diastolic blood pressure and HDL-cholesterol, but these genetic associations with blood pressure and HDL-cholesterol were attenuated after adjusting for alcohol use, suggesting the apparent genetic associations were possibly mediated by alcohol use. Conclusions ALDH2 variants are a credible genetic instrument for Mendelian randomization studies of alcohol use and many attributes of health in Southern Chinese men.