Genome-wide meta-analysis of problematic alcohol use yields insights into biology and relationships with other traits

A genome-wide analysis of more than 435,000 people has identified 29 genetic variants linked to problematic drinking, researchers at Yale University School of Medicine and colleagues report May 25 in the journal Nature Neuroscience.
Although genome-wide association studies have identified Problematic alcohol use (PAU) risk genes, the genetic architecture of this trait is not fully understood.
Researchers conducted a proxy-phenotype meta-analysis of problematic alcohol use, combining alcohol use disorder and problematic drinking, in 435,563 European ancestry individuals. As a result, 29  independent risk variants for problematic alcohol use were identified, 19 of which were previously unknown.
Problematic alcohol use was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n = 67,589) confirmed the genetic correlations between problematic alcohol use and substance use and psychiatric disorders. Genetic heritability of problematic alcohol use was enriched in brain and in conserved and regulatory genomic regions.
Using Mendelian randomisation, the researchers were able to investigate how one genetically influenced trait affects another genetically linked trait. The technique suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behaviour and cognitive performance.
In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other traits.
Hang Zhou, associate research scientist in psychiatry and lead author of the study commented, “This gives us ways to understand causal relations between problematic alcohol use traits such as psychiatric states, risk-taking behaviour, and cognitive performance.”
Joel Gelernter, the Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, commented that “With these results, we are also in a better position to evaluate individual-level risk for problematic alcohol use,” Gelernter said.
Source: Zhou, H., Sealock, J.M., Sanchez-Roige, S. et al. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nat Neurosci (2020).