Testing structural models of psychopathology at the genomic level

Area of Science:

• Psychiatric Genetics
• Computational Psychiatry
• Genomic Epidemiology

Background:

• Genome-wide association studies (GWAS) identify numerous genetic loci linked to psychiatric disorder vulnerability.
• Significant genetic correlations among disorders suggest a higher-order structure in psychopathology.
• Existing frameworks like the Hierarchical Taxonomy of Psychopathology (HiTOP) aim to clarify this structure.

Purpose of the Study:

• To investigate the genomic-level structure of psychopathology.
• To test multiple structural models using genetic correlations from GWAS summary statistics.
• To determine the best-fitting model for understanding the genetic underpinnings of psychiatric disorders.

Main Methods:

• Utilized GWAS summary statistics for fourteen psychiatric disorders and related traits.
• Estimated genetic correlations among these disorders.
• Applied structural modeling techniques to assess various psychopathology architectures.

Main Results:

• The best-fitting model identified four correlated higher-order genomic factors: externalizing, internalizing, thought problems, and neurodevelopmental disorders.
• These factors demonstrated distinct genetic correlation patterns with external validity variables.
• A bifactor model with a general psychopathology factor did not fit as well as the four-factor model.
• Eating disorders, obsessive-compulsive disorder, bipolar disorder, and schizophrenia were found to load together on the thought problems factor.

Conclusions:

• The findings support a four-dimensional genomic structure of psychopathology.
• This structure aligns with several higher-order dimensions proposed by the HiTOP framework.
• The study suggests that the genomic structure of psychopathology is similar to its phenotypic organization.