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.

26 August 2022 In General Health

AIMS: The Tromso Study 1979-1980 collected information on alcohol (beer, wine and spirits) consumption frequency and inebriation frequency, and the oldest male participants (aged 50-54 years) were followed for all-cause mortality. This study aimed to identify the impact of habitual alcohol consumption in mid-life on reaching up to 90 years of age.

RESULTS: Among the study sample of 778, a total of 120 (15.4%) men reached the age of 90. The most common reported alcohol consumption frequency was 'never or a few times a year', and 18.9% of those in this group reached 90 compared with 11.9% of those who reported a more frequent beer consumption. Fifty per cent survival in these groups was 80.5 and 76.9 years, respectively. The pattern was similar for spirits consumption and for inebriation but not for wine consumption. Number of deaths increased gradually with increasing beer and spirits consumption frequency and with inebriation frequency. We observed no J-shape or pattern that revealed a beneficial influence of light alcohol consumption. Daily smoking, physical inactivity, marital status, blood pressure and total cholesterol reduced the contribution of alcohol consumption to a small degree.

CONCLUSIONS: This study shows that all beer and spirits consumption frequencies in mid-life affect later life and total lifespan. Refraining from alcohol consumption or drinking only a few times a year increases one's chances of living longer, and the chance of reaching 90 years of age is 1.6-fold higher than in those with more frequent alcohol consumption.

26 August 2022 In General Health

Alcohol's impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption (n = 941,280) and alcohol use disorder (AUD) (n = 57,564 cases).

Non-linear MR employed UK Biobank individual data. MR analyses suggested a causal relationship between alcohol traits, more strongly for AUD, and telomere length. Higher genetically-predicted AUD (inverse variance-weighted (IVW) beta = -0.06, 95% confidence interval (CI): -0.10 to -0.02, p = 0.001) was associated with shorter telomere length. There was a weaker association with genetically-predicted alcoholic drinks weekly (IVW beta = -0.07, CI: -0.14 to -0.01, p = 0.03).

Results were consistent across methods and independent from smoking. Non-linear analyses indicated a potential threshold relationship between alcohol and telomere length. Our findings indicate that alcohol consumption may shorten telomere length. There are implications for age-related diseases.

26 August 2022 In General Health

BACKGROUND: Gamma-glutamyltransferase (GGT) levels in the blood can be a sensitive marker of liver injury but the extent to which they give insight into risk across multiple outcomes in a clinically useful way remains uncertain.

METHODS: Using data from 293,667 UK Biobank participants, the relationship of GGT concentrations to self-reported alcohol intake and adiposity markers were investigated. We next investigated whether GGT predicted liver-related, cardiovascular (CV) or all-cause mortality, and potentially improved CV risk prediction.

FINDINGS: Higher alcohol intake and greater waist circumference (WC) were associated with higher GGT; the association was stronger for alcohol with evidence of a synergistic effect of WC. Higher GGT concentrations were associated with multiple outcomes. Compared to a GGT of 14.5 U/L (lowest decile), values of 48 U/L for women and 60 U/L for men (common upper limits of 'normal') had hazard ratios (HRs) for liver-related mortality of 1.83 (95% CI 1.60-2.11) and 3.25 (95% CI 2.38-4.42) respectively, for CV mortality of 1.21 (95% CI 1.14-1.28) and 1.43 (95% CI 1.27-1.60) and for all-cause mortality of 1.15 (95% CI 1.12-1.18) and 1.31 (95% CI 1.24-1.38). Adding GGT to a risk algorithm for CV mortality reclassified an additional 1.24% (95% CI 0.14-2.34) of participants across a binary 5% 10-year risk threshold.

INTERPRETATION: Our study suggests that a modest elevation in GGT levels should trigger a discussion with the individual to review diet and lifestyle including alcohol intake and consideration of formal liver disease and CV risk assessment if not previously done.

FUNDING: British Heart Foundation Centre of Research Excellence Grant (grant number RE/18/6/34217), NHS Research Scotland (grant number SCAF/15/02), the Medical Research Council (grant number MC_UU_00022/2); and the Scottish Government Chief Scientist Office (grant number SPHSU17).

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