TY - JOUR
T1 - Testing structural models of psychopathology at the genomic level
AU - Waldman, Irwin D.
AU - Poore, Holly E.
AU - Luningham, Justin M.
AU - Yang, Jingjing
N1 - Funding Information:
Earlier versions of this work were presented at the 32nd Meeting of the Society for Research in Psychopathology and the 49th Meeting of the Behavior Genetics Association. The authors are grateful to the Consortia that made their GWAS summary statistics available, and would like to thank A. Grotzinger, M. Nivard and E. Tucker-Drob for their assistance in using their program Genomic-SEM to analyze the data. I.D. Waldman, H.E. Poore and J.M. Luningham contributed equally to this work.
Publisher Copyright:
© 2020 World Psychiatric Association
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Genome-wide association studies (GWAS) have revealed hundreds of genetic loci associated with the vulnerability to major psychiatric disorders, and post-GWAS analyses have shown substantial genetic correlations among these disorders. This evidence supports the existence of a higher-order structure of psychopathology at both the genetic and phenotypic levels. Despite recent efforts by collaborative consortia such as the Hierarchical Taxonomy of Psychopathology (HiTOP), this structure remains unclear. In this study, 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 included four correlated higher-order factors – externalizing, internalizing, thought problems, and neurodevelopmental disorders – which showed distinct patterns of genetic correlations with external validity variables and accounted for substantial genetic variance in their constituent disorders. A bifactor model including a general factor of psychopathology as well as the four specific factors fit worse than the above model. Several model modifications were tested to explore the placement of some disorders – such as bipolar disorder, obsessive-compulsive disorder, and eating disorders – within the broader psychopathology structure. The best-fitting model indicated that eating disorders and obsessive-compulsive disorder, on the one hand, and bipolar disorder and schizophrenia, on the other, load together on the same thought problems factor. These findings provide support for several of the HiTOP higher-order dimensions and suggest a similar structure of psychopathology at the genomic and phenotypic levels.
AB - Genome-wide association studies (GWAS) have revealed hundreds of genetic loci associated with the vulnerability to major psychiatric disorders, and post-GWAS analyses have shown substantial genetic correlations among these disorders. This evidence supports the existence of a higher-order structure of psychopathology at both the genetic and phenotypic levels. Despite recent efforts by collaborative consortia such as the Hierarchical Taxonomy of Psychopathology (HiTOP), this structure remains unclear. In this study, 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 included four correlated higher-order factors – externalizing, internalizing, thought problems, and neurodevelopmental disorders – which showed distinct patterns of genetic correlations with external validity variables and accounted for substantial genetic variance in their constituent disorders. A bifactor model including a general factor of psychopathology as well as the four specific factors fit worse than the above model. Several model modifications were tested to explore the placement of some disorders – such as bipolar disorder, obsessive-compulsive disorder, and eating disorders – within the broader psychopathology structure. The best-fitting model indicated that eating disorders and obsessive-compulsive disorder, on the one hand, and bipolar disorder and schizophrenia, on the other, load together on the same thought problems factor. These findings provide support for several of the HiTOP higher-order dimensions and suggest a similar structure of psychopathology at the genomic and phenotypic levels.
KW - Genome-wide association studies (GWAS)
KW - Hierarchical Taxonomy of Psychopathology (HiTOP)
KW - externalizing
KW - internalizing
KW - neurodevelopmental disorders
KW - psy-chological traits
KW - psychiatric disorders
KW - thought problems
UR - http://www.scopus.com/inward/record.url?scp=85090964299&partnerID=8YFLogxK
U2 - 10.1002/wps.20772
DO - 10.1002/wps.20772
M3 - Article
AN - SCOPUS:85090964299
SN - 1723-8617
VL - 19
SP - 350
EP - 359
JO - World Psychiatry
JF - World Psychiatry
IS - 3
ER -