Genetic overlap influences comorbidity of PAU, psychiatric disorders

Some shared genetic factors can affect the comorbidity of problematic alcohol use (PAU) and psychiatric disorders, according to a study. Specifically, TTC12 and ANKK1 show a potentially causal association with comorbid conditions.

Analysis using a bivariate causal mixture model (MiXeR) revealed a significant polygenic overlap (39 percent to 73 percent) between PAU and psychiatric disorders. Four bivariate genomic regions with high correlations indicated shared causal variants of PAU with schizophrenia and major depression.

Conjunctional false discovery rate (FDR) analysis mapped four genes for the PAU–major depression pair and six for the PAU-schizophrenia pair within the said regions. Additionally, the researchers identified TTC12 and ANKK1 as potential causal genes for PAU and these disorders. They replicated these findings in multi-ancestry analyses of colocalization and transcriptome-wide associations studies (TWASs).

This study used genome-wide association data of PAU, including 435,563 samples from people of European ancestry, to examine the genetic relationship between PAU and 11 psychiatric disorders via a bivariate causal MiXeR.

The researchers identified genomic regions associated with PAU and psychiatric disorders through local genetic correlation and colocalization analyses. They also performed a postanalysis, including FDR and TWAS, and a summary-data-based Mendelian randomization to prioritize shared genes by integrating brain transcriptome data.

“PAU adversely affects the clinical course of psychiatric disorders,” the researchers said. “Genetic studies have suggested that genetic factors underlie the co-occurrence of PAU with psychiatric disorders.”