In a recent article published in The Lancet, researchers investigate the associations of cause-specific mortality with alcohol intake using data from 512,724 Chinese adults (210,205 men and 302,519 women) registered in the China Kadoorie Biobank cohort.
Since two genetic variants, viz., ALDH2-rs671 and ADH1B-rs1229984, affect alcohol metabolism and tolerability in East Asian populations, they used genetic analysis using the Mendelian randomization (MR) approach alongside conventional observational analysis to assess the strength, shape, and causal relevance of genotype-predicted alcohol intake with cause-specific mortality.
Study: Alcohol intake and cause-specific mortality: conventional and genetic evidence in a prospective cohort study of 512 000 adults in China. Image Credit: 5PH/Shutterstock.com
Excessive alcohol use caused an estimated three million deaths worldwide in 2016, suggesting the burden of alcohol intake-related deaths is high and rising.
Researchers thoroughly searched the PubMed database from inception to Feb 25, 2023, for English language publications, especially MR studies on all-cause mortality due to alcohol use.
They found two MR studies done in populations with European ancestry and Chinese men reporting that higher alcohol intake was associated with higher risks of all-cause mortality. However, these studies did not assess causal relevance across different alcohol intakes.
Only conventional observational studies conducted in high-income countries (HICs) with large sample sizes have estimated the burden of alcohol intake-related deaths.
However, in these studies, the observed associations did not reflect causal effects, and their results were also susceptible to bias from residual confounding and reverse causation.
Thus, assessing the causal relevance of alcohol for death due to cardiovascular diseases (CVDs) and other diseases, e.g., cancer, could inform policies for the prevention of alcohol-induced hazards to health.
About the study
The study cohort, comprising men and women aged 30–79 years with no disability at enrolment, was recruited from ten areas of China from 2004–2008.
At study initiation, participants completed a questionnaire inquiring about their sociodemographic, lifestyle, and medical history. The team also collected blood samples and measured their blood pressure (BP) and anthropometry measurements.
Resurveys covered ~5% of surviving study participants. They averaged alcohol intakes at two resurveys to estimate the average alcohol intake per group.
Based on self-reported alcohol drinking patterns, the researchers classified participants into current drinkers, non-drinkers, occasional drinkers, and ex-drinkers.
For current drinkers, they also collected data on drinking frequency, amount, and beverage type and classified their weekly alcohol intake as <70 or ≥70 g/week for women and <140, 140–279, 280–419, or ≥420 g/week for men.
Furthermore, the researchers ascertained cause-specific mortality and grouped death into broad categories based on the International Classification of Diseases, tenth revision (ICD-10).
They used Cox proportional hazards regression models to examine the association between alcohol intake (predictor variable) and the time taken for an event to happen (disease or death, loss to follow-up), wherein they stratified participants based on age and geographical areas to account for the potential confounding effects.
These models also controlled for factors such as education and physical activity levels, household income, smoking status, fresh fruit intake, and genomic principal components controlling for population structure and ancestry.
The researchers used a weighted linear regression analysis to estimate the hazard ratio (HR) per 100 g/week of usual alcohol intake, which represented the relative risk of developing a disease or health condition associated with a specific level of alcohol intake.
The researchers plotted the log HRs against the average alcohol intake in each genotype-predicted alcohol intake category and supplemental analyses using a polygenic score. Beta estimates of the polygenic score in men were applied to the polygenic scores in women to assess pleiotropy.
The study cohort comprised more women than men; men tended to be current drinkers, while women tended to drink occasionally.
During 12 year of follow-up, Chinese death registries recorded 56,550 deaths, including 23,457 deaths among 168,050 participants genotyped for ALDH2-rs671 and ADH1B-rs1229984, which resulted in 151,347 individuals in genetic analyses and 16,703 people in case-control studies of CVD or chronic obstructive pulmonary disease (COPD).
Combining the two genetic variants, ALDH2-rs671 and ADH1B-rs1229984, predicted a 60-fold difference in mean alcohol intake ranging from 4 g/week in the lowest to 255 g/week in the highest category in men but no significant differences in women.
In separate genetic analyses using a polygenic score, these associations remained similar across different alcohol intakes.
In men, CVD and cancer accounted for most deaths, and the risk was higher in ex-drinkers, non-drinkers, and heavy drinkers compared to moderate drinkers.
Among women, alcohol intake was low in this study. Thus, there were no excess risks of cause-specific mortality, but there were lower risks of deaths from other medical causes, e.g., diabetes.
So, while alcohol mediated higher risks in men, the pleiotropic effects of the genotypes studied had no role to play in the observed effects.
In the present study, alcohol was likely causally associated with deaths from several major causes linearly and gradually in men but not women; thus, it accounted for ~7–8% of male deaths in this Chinese population.
The risk was high even among moderate drinkers consuming 10–20 g/day. Moreover, there were continuous positive associations with major causes of death (except for respiratory diseases) even at lower intakes among male drinkers, with no evidence of a threshold below which alcohol was unrelated to risk.
The study data could help devise new policies emphasizing guidance for low-risk alcohol drinking at a threshold of one to two drinks per week.