22 September 2022 In Dementia

Alcohol consumption has been associated with the risk of mild cognitive impairment (MCI) in observational studies. The result is inconsistent and whether the association is causal remains unknown. To examine the causal effect of alcohol consumption on MCI in rural China, this study used a cross-sectional dataset that included 1966 observations collected in rural China, of which 235 observations' genotyping were collected. All participants accepted the MCI evaluation using Mini-Cog and were asked about the participants' alcohol consumption behavior. The causal effect of alcohol consumption on MCI was investigated by Mendelian randomization (MR) of genetic variation in the aldehyde dehydrogenase 2 (ALDH2 rs671) gene. The risk of MCI in Chinese rural areas was 43%. Alcohol consumption was causally associated with a higher risk of MCI under MR design. Parameter estimates of drinking or not (b = 0.271, p = 0.007, 95% CI = 0.073 to 0.469), drinking frequency during the past 30 days (b = 0.016, p = 0.003, 95% CI = 0.005 to 0.027), and the weekly ethanol consumption (b = 0.132, p = 0.004, 95% CI = 0.042 to 0.223) were all positive and statistically significant at the 5% level. In conclusion, there was a high risk of MCI in rural China, and alcohol consumption was causally associated with a higher risk of MCI.

26 August 2022 In General Health

Alcohol consumption is associated with the development of cardiovascular diseases, cancer, and liver disease. The biological mechanisms are still largely unclear. Here, we aimed to use an agnostic approach to identify phenotypes mediating the effect of alcohol on various diseases.

METHODS: We performed an agnostic association analysis between alcohol consumption (red and white wine, beer/cider, fortified wine, and spirits) with over 7800 phenotypes from the UK biobank comprising 223,728 participants. We performed Mendelian randomisation analysis to infer causality. We additionally performed a Phenome-wide association analysis and a mediation analysis between alcohol consumption as exposure, phenotypes in a causal relationship with alcohol consumption as mediators, and various diseases as the outcome.

RESULTS: Of 45 phenotypes in association with alcohol consumption, 20 were in a causal relationship with alcohol consumption. Gamma glutamyltransferase (GGT; beta = 9.44; 95% CI = 5.94, 12.93; Pfdr = 9.04 x 10(-7)), mean sphered cell volume (beta = 0.189; 95% CI = 0.11, 0.27; Pfdr = 1.00 x 10(-4)), mean corpuscular volume (beta = 0.271; 95% CI = 0.19, 0.35; Pfdr = 7.09 x 10(-10)) and mean corpuscular haemoglobin (beta = 0.278; 95% CI = 0.19, 0.36; Pfdr = 1.60 x 10(-6)) demonstrated the strongest causal relationships. We also identified GGT and physical inactivity as mediators in the pathway between alcohol consumption, liver cirrhosis and alcohol dependence.

CONCLUSION: Our study provides evidence of causality between alcohol consumption and 20 phenotypes and a mediation effect for physical activity on health consequences of alcohol consumption.

22 March 2022 In Liver Disease

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk.

METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (>/=80 g/day (men), >/=50 g/day (women), for >/=10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC).

RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 +/- 0.06 vs. 0.61 +/- 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption.

CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions.

LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

03 June 2019 In Cancer

Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in differences between individuals in exposure to acetaldehyde, leading to possible carcinogenic effects. Arg47His (rs1229984 G > A) in ADH1B have been frequently studied for its potential effect on carcinogenesis. However, the findings are as yet inconclusive. To gain a more precise estimate of this potential association, we conducted a meta-analysis including 66 studies from 64 articles with 31999 cases and 50964 controls. The pooled results indicated that ADH1B Arg47His polymorphism is significantly associated with the decreased risk of overall cancer (homozygous model, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.49-0.77; heterozygous model, OR = 0.71, 95% CI = 0.60-0.84; recessive model, OR = 0.83, 95% CI = 0.76-0.91; dominant model, OR = 0.62, 95% CI = 0.53-0.72; and allele comparison, OR = 0.82, 95% CI = 0.75-0.89). Stratified analysis by cancer type and ethnicity showed that a decreased risk was associated with esophageal cancer and head and neck cancer amongst Asians. In conclusion, our meta-analysis suggested that ADH1B Arg47His polymorphism was significantly associated with decreased overall cancer risk. These findings need further validation in large multicenter investigations.

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