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We read with interest findings of a genome-wide association study (GWAS) in the UK Biobank reported by Clarke et al1 in Molecular Psychiatry. The authors aimed to conduct a GWAS of alcohol consumption. Prior to conducting the GWAS, Clarke and colleagues regressed alcohol intake on body weight and age, and used the residuals from this regression analysis for the GWAS analysis. The authors identified 14 loci harbouring variants associated with the residuals at levels indicative of GWAS significance and took these forward to characterise the relationship of these SNPs with various phenotypes, such as adiposity.

Problems in interpreting and using GWAS of conditional phenotypes illustrated by 'alcohol GWAS'