Relationship Between Problematic Alcohol Use and Various Psychiatric Disorders: A Genetically Informed Study.

Area of Science:

• Genetics
• Psychiatry
• Neuroscience

Background:

• Problematic alcohol use (PAU) negatively impacts psychiatric disorder progression.
• Genetic factors are implicated in the co-occurrence of PAU and psychiatric conditions.
• Understanding shared genetic architectures is crucial for identifying common etiological pathways.

Purpose of the Study:

• To elucidate shared genetic architectures between PAU and 11 psychiatric disorders.
• To prioritize genes potentially common to PAU and psychiatric conditions.
• To investigate the genetic relationship using genome-wide association data.

Main Methods:

• Utilized genome-wide association data from 435,563 individuals of European ancestry for PAU.
• Employed a bivariate causal mixture model (MiXeR) to assess genetic relationships.
• Conducted local genetic correlation, colocalization, FDR, TWAS, and Mendelian randomization analyses.

Main Results:

• Demonstrated substantial polygenic overlap (39%-73%) between PAU and psychiatric disorders.
• Identified four genomic regions with high correlations suggesting shared causal variants for PAU with major depression and schizophrenia.
• Pinpointed TTC12 and ANKK1 as potential causal genes for PAU and comorbid psychiatric disorders, with findings replicated across ancestries.

Conclusions:

• Confirmed the presence of shared genetic factors contributing to the comorbidity of PAU and psychiatric disorders.
• Highlighted TTC12 and ANKK1, near DRD2, as potentially causal genes for these comorbid conditions.
• Emphasized the importance of genetic insights for understanding complex psychiatric comorbidities.