DOI: 10.1101/502039Apr 28, 2020Paper

Testing Structural Models of Psychopathology at the Genomic Level

BioRxiv : the Preprint Server for Biology
Justin M LuninghamIrwin D Waldman


Genome wide association studies (GWAS) have revealed hundreds of genetic loci that underlie major psychiatric disorders, and post-GWAS analyses have discovered substantial genetic correlations among these disorders. This suggests these disorders share a common genetic architecture, implying the presence of a higher order structure of psychopathology at both the genetic and phenotypic levels. Nonetheless, despite recent efforts at elucidating this structure by collaborative consortia such as HiTOP, the exact structure of psychopathology remains unknown. Herein, in one of the largest genetic studies of psychopathology conducted to date, we tested multiple alternative structural models of psychopathology at the genomic level using the genetic correlations among fourteen psychiatric disorders and related psychological traits estimated from GWAS summary statistics. The best fitting model includes four correlated higher order factors: Externalizing, Internalizing, Thought Problems, and Neurodevelopmental Disorders. These higher order factors were validated by examining their correlations with external criterion variables, which showed distinct patterns of genetic correlations with the 4 higher order factors. Several model modificatio...Continue Reading

Related Concepts

Mental Disorders
Genetic Loci
Neurodevelopmental Disorders
Genome Assembly Sequence
Genome-Wide Association Study

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