A common genetic aetiology may explain some of the overlap between alcohol dependence and cognitive impairment. The estimated heritabilities for alcohol dependence and adult general cognitive ability range from ∼40 to 70 percent (Enoch & Goldman 2001; Haworth et al. 2010; Calvin et al. 2012); however, few studies have examined their genetic overlap. One established approach to detect shared genetic effects between traits is to use polygenic risk profiling (Purcell et al. 2009; Evans et al. 2013). Summary data from a genome‐wide association study (GWAS) of a disease of interest is used to determine the weighted number of risk alleles an individual in an independent sample carries. Polygenic risk profiles thus denote an individual's genetic load for a particular disorder. By testing the association between a polygenic risk score (PGRS) for alcohol dependence and potential biological intermediates (cognitive ability), we are able to analyse the relationship between the two traits without having to measure alcohol dependence directly in the cohort being studied. Furthermore, associations between polygenic risk profiles and biological intermediates will not be confounded by environmental exposures and may highlight potentially causal pathways which warrant further study (Evans et al. 2013).
