Polygenic risk scores in imaging genetics: Usefulness and applications

Area of Science:

• Psychiatric genetics
• Neuroscience
• Computational biology

Background:

• Genetic factors significantly contribute to schizophrenia and bipolar disorder liability (up to 80%).
• Genome-wide association studies (GWAS) have identified numerous risk-associated single nucleotide polymorphisms (SNPs) and genes.
• Individual SNP effects are small, necessitating approaches that capture the cumulative impact of many genetic variants.

Purpose of the Study:

• To highlight the utility of polygenic risk scores (PRS) in psychiatric research.
• To advocate for the integration of PRS into imaging genetics studies.
• To enhance risk prediction, intervention, and personalized medicine for psychiatric disorders.

Main Methods:

• Utilizing polygenic risk score (PRS) modeling to aggregate effects of risk-associated alleles.
• Leveraging large-scale GWAS data for robust PRS calculation, applicable even in smaller sample sizes.
• Proposing the combination of PRS with neuroimaging data in imaging genetics research.

Main Results:

• PRS models the aggregate genetic risk for complex psychiatric disorders.
• PRS enables the application of large GWAS findings to smaller, focused studies.
• The cumulative effect of numerous genetic variants underlies the polygenic architecture of these disorders.

Conclusions:

• Polygenic risk scores offer a powerful tool for understanding the genetic basis of schizophrenia and bipolar disorder.
• Integrating PRS into imaging genetics research can significantly advance risk prediction and personalized treatment strategies.
• PRS are crucial for a comprehensive approach to psychiatric disorder research and clinical application.