Evidence for strong genetic correlations among internalizing psychopathology and related self-reported measures using both genomic and twin/adoptive approaches

J Psychopathol Clin Sci. 2024 May 9. doi: 10.1037/abn0000905. Online ahead of print.

Abstract

The internalizing construct captures shared variance underlying risk for mood and anxiety disorders. Internalizing factors based on diagnoses (or symptoms) of major depressive disorder (MDD) and generalized anxiety disorder (GAD) are well established. Studies have also integrated self-reported measures of associated traits (e.g., questionnaires assessing neuroticism, worry, and rumination) onto these factors, despite having not tested the assumption that these measures truly capture the same sets of risk factors. This study examined the overlap among both sets of measures using converging approaches. First, using genomic structural equation modeling, we constructed internalizing factors based on genome-wide association studies (GWASs) of internalizing diagnoses (e.g., MDD) and traits associated with internalizing (neuroticism, loneliness, and reverse-scored subjective well-being). Results indicated the two factors were highly (rg = .79) but not perfectly genetically correlated (rg < 1.0, p < .001). Second, we constructed similar latent factors in a combined twin/adoption sample of adults from the Colorado Adoption/Twin Study of Lifespan Behavioral Development and Cognitive Aging. Again, both factors demonstrated strong overlap at the level of genetic (rg = .76, 95% confidence interval [CI] [0.40, 0.97]) and nonshared environmental influences (re = .80, 95% CI [0.53, 1.0]). Shared environmental influences were estimated near zero for both factors. Our findings are consistent with current frameworks of psychopathology, though they suggest there are some unique genetic influences captured by internalizing diagnosis compared to trait measures, with potentially more nonadditive genetic influences on trait measures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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