What is the effect of alcohol consumption on the risk of chronic widespread pain? A Mendelian randomisation study using UK Biobank

Studies have shown that moderate alcohol consumption is strongly associated with reduced reporting of chronic widespread pain (CWP). The study designs used however are prone to confounding and are not able to establish the direction of causality. The current study overcomes these problems by using the Mendelian randomisation design to determine the effect of alcohol consumption on the likelihood of reporting CWP. The UK Biobank recruited 500,000 participants aged between 40 and 69 years. Data collected included questions on chronic pain and alcohol consumption, and biological samples providing genotypic information. Alcohol consumption was categorised as 'weekly consumption' or 'non or infrequent'. Participants were classified by genotype according to alleles of the rs1229984 SNP, either 'GG' or 'AA/AG'. CWP was defined as pain all over the body for more than 3 months that interfered with activities. Associations between genotype, CWP and alcohol consumption were tested by logistic regression. Instrumental variable analysis was used to calculate the causal effect of weekly alcohol consumption on CWP. Persons with 'GG' genotype had an increased risk of CWP (odds ratio, OR 1.17, 99% confidence interval CI 1.01-1.35) and were more likely to consume alcohol weekly (OR 1.76, 1.70-1.81) compared to those with 'AA/AG' genotype. Weekly consumption of alcohol was associated with reduced risk of CWP (OR 0.33, 0.31-0.35), but instrumental variable analysis did not show a causal effect of alcohol consumption on reducing CWP (OR 1.29, 0.96-1.74). An interpretation of observational population studies as showing a protective effect of alcohol on CWP is not supported.