title: Mendelian randomization estimates of alanine aminotransferase with cardiovascular disease: Guangzhou Biobank Cohort study.
abstract: Observational studies of the association of alanine aminotransferase (ALT) levels with ischaemic heart disease (IHD) and cardiovascular disease (CVD) risk factors are inconsistent, probably because of confounding and reverse causality. Mendelian randomization (MR) provides less confounded results. We used MR analysis to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors. We used instrumental variable analysis based on two single nucleotide polymorphism (SNPs) HSD17B13/MAPK10 (rs6834314) and PNPLA3/SAMM50 (rs738409) to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors in the Guangzhou Biobank Cohort Study (GBCS). Observationally in 19,925 participants ALT levels were strongly positively associated with self-reported IHD, systolic and diastolic blood pressure, low-density lipoprotein- and total cholesterol, triglycerides, fasting glucose, body mass index, waist circumference, heart rate (HR) and diabetes, but were not associated with uncorrected QT interval, HR-corrected QT interval or high-density lipoprotein-cholesterol. In the MR study, using a credible genetic instrument (F-statistic = 23) for ALT, ALT levels were negatively associated with IHD (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.87 to 0.97) and triglycerides (β - 0.08, 95% CI - 0.13 to - 0.03), but were not associated with other CVD risk factors. Our results using Mendelian randomization suggest that ALT reduces the risk of IHD, probably through reducing triglyceride levels. The underlying mechanisms deserve further investigation.
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Guangzhou 12th Hospital, Guangzhou, People's Republic of China.
authors.forename: Chao Qiang
authors.initials: CQ
authors.lastname: Jiang
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.|Guangzhou 12 Hospital, Guangzhou, People's Republic of China.
authors.forename: Tai Hing
authors.initials: TH
authors.lastname: Lam
authors.affiliation: Guangzhou 12th Hospital, Guangzhou, People's Republic of China.
authors.forename: Wei Sen
authors.initials: WS
authors.lastname: Zhang
authors.affiliation: Guangzhou 12th Hospital, Guangzhou, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Guangzhou 12th Hospital, Guangzhou, People's Republic of China.
authors.forename: Ya Li
authors.initials: YL
authors.lastname: Jin
authors.affiliation: Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
authors.affiliation: Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
authors.forename: Kar Keung
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.|CUNY School of Public Health at Hunter College, 2180 Third Avenue, New York, NY, USA.
authors.forename: C Mary
authors.initials: CM
authors.lastname: Schooling
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000235:genetics*; D018070:Biological Specimen Banks; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008049:Lipase / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D057182:Mendelian Randomization Analysis; D048057:Mitogen-Activated Protein Kinase 10; D017202:Myocardial Ischemia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D008049:Lipase; D008565:Membrane Proteins; D048057:Mitogen-Activated Protein Kinase 10; D014280:Triglycerides; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent