Phenotypic and genetic markers of psychopathology in a population-based sample of older adults.

TitlePhenotypic and genetic markers of psychopathology in a population-based sample of older adults.
Publication TypeJournal Article
Year of Publication2021
AuthorsGard, AM, Ware, EB, Hyde, LW, Schmitz, LL, Faul, JD, Mitchell, CM
JournalTranslational Psychiatry
Volume11
Issue1
Pagination239
ISSN Number2158-3188
KeywordsGenetic Markers, Phenotypic markers, psychopathology
Abstract

Although psychiatric phenotypes are hypothesized to organize into a two-factor internalizing-externalizing structure, few studies have evaluated the structure of psychopathology in older adults, nor explored whether genome-wide polygenic scores (PGSs) are associated with psychopathology in a domain-specific manner. We used data from 6003 individuals of European ancestry from the Health and Retirement Study, a large population-based sample of older adults in the United States. Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered genome-wide association studies (GWAS). Genomic SEM was implemented to construct latent PGSs for internalizing, externalizing, and general psychopathology. Phenotypically, the data were best characterized by a single general factor of psychopathology, a factor structure that was replicated across genders and age groups. Although externalizing PGSs (cannabis use, antisocial behavior, alcohol dependence, attention deficit hyperactivity disorder) were not associated with any phenotypes, PGSs for major depressive disorder, neuroticism, and anxiety disorders were associated with both internalizing and externalizing phenotypes. Moreover, the variance explained in the general factor of psychopathology increased by twofold (from 1% to 2%) using the latent internalizing or latent one-factor PGSs, derived using weights from Genomic Structural Equation Modeling (SEM), compared with any of the individual PGSs. Collectively, results suggest that genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in older adults of European ancestry. Alternative explanations are discussed, including methodological limitations of GWAS and phenotypic measurement of psychiatric outcome in large-scale population-based studies.

DOI10.1038/s41398-021-01354-2
Citation Key11589
PubMed ID33895785
Grant ListR01 MH121079 / MH / NIMH NIH HHS / United States
R01 MH110872 / MH / NIMH NIH HHS / United States
R01 MD011716 / MD / NIMHD NIH HHS / United States
R01-AG055406 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01-AG055654a / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
L60-MD012145 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
P30-AG012846 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
K99-AG05659 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
P30-AG012846 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01-AG055406 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01-AG055654a / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /