CONTEXT: Effects of modest alcohol consumption remain controversial. Mendelian randomization (MR) can help to mitigate biases due to confounding and reverse causation in observational studies, and evaluate the potential causal role of alcohol consumption.
OBJECTIVE: This work aimed to evaluate dose-dependent effect of alcohol consumption on obesity and type 2 diabetes.
METHODS: Assessing 408 540 participants of European ancestry in the UK Biobank, we first tested the association between self-reported alcohol intake frequency and 10 anthropometric measurements, obesity, and type 2 diabetes. We then conducted MR analyses both in the overall population and in subpopulations stratified by alcohol intake frequency.
RESULTS: Among individuals having more than 14 drinks per week, a 1-drink-per-week increase in genetically predicted alcohol intake frequency was associated with a 0.36-kg increase in fat mass (SD = 0.03 kg), a 1.08-fold increased odds of obesity (95% CI, 1.06-1.10), and a 1.10-fold increased odds of type 2 diabetes (95% CI, 1.06-1.13). These associations were stronger in women than in men. Furthermore, no evidence was found supporting the association between genetically increased alcohol intake frequency and improved health outcomes among individuals having 7 or fewer drinks per week, as MR estimates largely overlapped with the null. These results withstood multiple sensitivity analyses assessing the validity of MR assumptions.
CONCLUSION: As opposed to observational associations, MR results suggest there may not be protective effects of modest alcohol consumption on obesity traits and type 2 diabetes. Heavy alcohol consumption could lead to increased measures of obesity as well as increased risk of type 2 diabetes.
BACKGROUND AND AIMS: We investigated the causal relevance of alcohol intake with measures of carotid artery thickness and atherosclerosis in Chinese adults.
METHODS: The study included 22,384 adults from the China Kadoorie Biobank, with self-reported alcohol use at baseline and resurvey, carotid artery ultrasound measurements, and genotyping data for ALDH2-rs671 and ADH1B-rs1229984. Associations of carotid intima media thickness (cIMT), any carotid plaque, and total plaque burden (derived from plaque number and size) with self-reported (conventional analyses) and genotype-predicted mean alcohol intake (Mendelian randomization) were assessed using linear and logistic regression models.
RESULTS: Overall 34.2% men and 2.1% women drank alcohol regularly at baseline. Mean cIMT was 0.70 mm in men and 0.64 mm in women, with 39.1% and 26.5% having carotid plaque, respectively. Among men, cIMT was not associated with self-reported or genotype-predicted mean alcohol intake. The risk of plaque increased significantly with self-reported intake among current drinkers (odds ratio 1.42 [95% CI 1.14-1.76] per 280 g/week), with directionally consistent findings with genotype-predicted mean intake (1.21 [0.99-1.49]). Higher alcohol intake was significantly associated with higher carotid plaque burden in both conventional (0.19 [0.10-0.28] mm higher per 280 g/week) and genetic analyses (0.09 [0.02-0.17]). Genetic findings in women suggested the association of genotype-predicted alcohol with carotid plaque burden in men was likely to due to alcohol itself, rather than pleiotropic genotypic effects.
CONCLUSIONS: Higher alcohol intake was associated with a higher carotid plaque burden, but not with cIMT, providing support for a potential causal association of alcohol intake with carotid atherosclerosis.
PURPOSE: Previous observational studies have shown that alcohol and coffee were associated with colorectal cancer (CRC) risk, but the causal relationships have not been adequately explored. This study aimed to assess the potential causal associations of alcohol and coffee with CRC risk using Mendelian randomization (MR) analyses in an East Asian population.
METHODS: Publicly available summary-level genome-wide association studies data on ever/never alcohol drinker (n = 165,084), alcohol consumption (n = 58,610), coffee consumption (n = 152,634), and CRC (7062 cases and 195,745 controls) were obtained from the BioBank Japan (BBJ). Single-nucleotide polymorphisms (SNPs) that were significantly related to the exposures were identified as instrumental variables.
Five, two, and six SNPs were used for ever/never alcohol drinkers, alcohol consumption, and coffee consumption, respectively. The inverse variance weighted method was used as the main MR method to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of CRC risk per one-unit change in exposures.
RESULTS: Genetically predicted ever/never alcohol drinkers (OR: 1.08; 95% CI 1.06, 1.11; P < 0.001) and alcohol consumption (OR: 1.39; 95% CI 1.21, 1.60; P < 0.001) were positively associated with CRC risk. Conversely, genetically predicted coffee consumption was inversely related to CRC risk, with an OR (95% CI) of 0.80 (0.64, 0.99) (P = 0.037). CONCLUSION: Genetically predicted alcohol use and consumption were risk factors for CRC while genetically predicted coffee consumption was a protective factor.
Our findings highlight the effectiveness of keeping healthy dietary habits to prevent CRC. Further studies with more valid SNPs and CRC cases are needed. Validation of our findings is also recommended.
BACKGROUND: The causal effects of moderate alcohol consumption on cardiovascular diseases (CVDs) are continuously debated, especially on coronary artery disease (CAD).
OBJECTIVES: We aimed to explore the causal associations of alcohol consumption with CVDs and all-cause mortality among Chinese males.
METHODS: A prospective cohort study was conducted in 40,386 Chinese males, with 17,676 being genotyped for the rs671 variant in the aldehyde dehydrogenase 2 (ALDH2) gene. A Cox proportional hazards model was conducted to estimate the effects of self-reported alcohol consumption. Mendelian randomization (MR) analysis was performed to explore the causality using rs671 as an instrumental variable. RESULTS: During the follow-up of 303,353 person-years, 2406 incident CVDs and 3195 all-cause mortalities were identified. J-shaped associations of self-reported alcohol consumption with incident CVD and all-cause mortality were observed, showing decreased risks for light (</=25 g/d) and moderate drinkers (25-</=60 g/d). However, MR analyses revealed a linear association of genetically predicted alcohol consumption with the incident CVD (P-trend = 0.02), including both CAD (P-trend = 0.03) and stroke (P-trend = 0.02). The HRs (95% CIs) for incident CVD across increasing tertiles of genetically predicted alcohol consumption were 1 (reference), 1.18 (1.01, 1.38), and 1.22 (1.03, 1.46). After excluding heavy drinkers, the risk of incident CVD and all-cause mortality was increased by 27% and 20% per standard drink increment of genetically predicted alcohol consumption, respectively.
CONCLUSIONS: Our analyses extend the evidence of the harmful effect of alcohol consumption to total CVD (including CAD) and all-cause mortality, highlighting the potential health benefits of lowering alcohol consumption, even among light-to-moderate male drinkers.