Specificity of Psychiatric Polygenic Risk Scores and Their Effects on Associated Risk Phenotypes

Area of Science:

• Psychiatric Genetics
• Biostatistics
• Neuroscience

Background:

• Polygenic risk scores (PRSs) assess genetic liability for illness.
• Current clinical utility of PRSs for specific psychiatric disorders is limited.
• Genetic overlap among disorders and their effects on allied phenotypes may explain limitations but is difficult to quantify.

Purpose of the Study:

• To construct PRSs for five psychiatric disorders and three control traits.
• To quantify associations between PRSs and behavioral and brain phenotypes.
• To evaluate the specificity of PRSs and their effects on allied phenotypes.

Main Methods:

• Constructed PRSs for schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and ADHD.
• Included height, type II diabetes, and irritable bowel disease as control traits.
• Utilized UK Biobank data (N=31,616) and analyzed associations with behavioral and neuroimaging phenotypes.

Main Results:

• Replicated correlations among psychiatric PRSs, showing distinct overlaps (e.g., schizophrenia/bipolar disorder, ASD/ADHD).
• Observed minimal overlap between psychiatric and control PRSs.
• Found substantial, phenotype-specific overlap in PRS effects on allied phenotypes across psychiatric and control traits.

Conclusions:

• Genetic distinctions exist between psychiatric disorders and control traits.
• These distinctions do not fully translate to specific effects on allied phenotypes.
• Further development of PRSs is required for clinical application specificity.