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. 2025 Dec;16(1):2463187.
doi: 10.1080/20008066.2025.2463187. Epub 2025 Feb 12.

Using genomic structural equation modeling to examine the genetic architecture of PTSD and life satisfaction phenotypes

Shannon E Cusack  1 , Anna W Wright  2 , Peter B Barr  3 , Emily Notari  4 , Kaitlin E Bountress  1 , Ananda B Amstadter  1
Affiliations

Using genomic structural equation modeling to examine the genetic architecture of PTSD and life satisfaction phenotypes

Shannon E Cusack et al. Eur J Psychotraumatol. 2025 Dec.

Abstract
in English, Spanish

Objective: Posttraumatic stress disorder (PTSD) and life satisfaction phenotypes are inversely related on a phenotypic level. Given these established relations, researchers have begun to examine possible shared genetic contributions to these outcomes, though the existing genetic literature is sparse and examines these relations via univariate methods. We sought to examine the genetic architecture of PTSD and six life satisfaction and well-being phenotypes (i.e. subjective well-being, friend satisfaction, life satisfaction, family satisfaction, work satisfaction, and financial satisfaction) using a multivariate approach.Method: We used Genomic Structural Equation Modeling (gSEM) to analyze summary-level genetic data from large-scale GWAS of the European Ancestry.Results: Findings show that a two, correlated factors model fit the data best, in which PTSD and life satisfaction phenotypes load on separate but correlated factors.Conclusions: Findings suggest that, using multivariate methods, a latent factor capturing many different positive phenotypes is genetically related to PTSD. This finding confirms and extends prior phenotypic work demonstrating that PTSD and positive phenotypes are inversely related.

Objetivo: El Trastorno de estrés postraumático (TEPT) y los fenotipos de satisfacción con la vida están inversamente relacionados a nivel fenotípico. Dada estas relaciones establecidas, los investigadores han comenzado a examinar las posibles contribuciones genéticas compartidas a estos resultados, aunque la literatura genética existente es escasa y examina estas relaciones mediante de métodos univariados. Buscamos examinar la arquitectura genética del TEPT y seis fenotipos de satisfacción con la vida y bienestar (ej., bienestar subjetivo, satisfacción con los amigos, satisfacción con la vida, satisfacción familiar, satisfacción laboral y satisfacción financiera/económica utilizando un enfoque multivariado.

Método: Utilizamos el Modelado de Ecuaciones Estructurales Genómicas (gSEM) para analizar los datos genéticos a nivel de resumen de GWAS a gran escala de la Ascendencia Europea.

Resultados: Los hallazgos muestran que un modelo de dos factores correlacionados se ajusta mejor a los datos, en el que los fenotipos de TEPT y de satisfacción con la vida se cargan en factores separados pero correlacionados.

Conclusiones: Los hallazgos sugieren que, utilizando métodos multivariados, un factor latente que capta muchos fenotipos positivos distintos está genéticamente relacionado con el TEPT. Este hallazgo confirma y amplia el trabajo fenotípico previo que demuestra que el TEPT y los fenotipos positivos están inversamente relacionados.

Keywords: Genomic structural equation modelling; Modelado de ecuaciones estructurales genómicas; genetics; life satisfaction; posttraumatic stress disorder; satisfacción con la vida; trastorno de estrés postraumático.

Plain language summary

PTSD and various life satisfaction phenotypes are genetically related but load on separate, correlated factors, as revealed through Genomic Structural Equation Modeling (gSEM).A two-factor model best explained the genetic architecture, suggesting distinct but interrelated genetic influences on PTSD and life satisfaction.These findings align with prior research, indicating a shared genetic basis between PTSD and positive phenotypes using a multivariate approach.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Two-correlated factor model with residual correlations model of life satisfaction and well-being phenotypes and PTSD.
Figure 2.
Figure 2.
Observed Correlations and Model-Implied Correlations. Note. Panel one represents the observed correlations and panel two the model implied correlations. The correlation coefficients (rg) are depicted on the upper triangle of each of the three matrices. The Z-scores are presented on the lower triangle. For the first panel (i.e. observed correlations), the SNP based heritability estimate (h2) is presented on the diagonal.
See this image and copyright information in PMC

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