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Predicting Cognitive Executive Functioning with Polygenic Risk Scores for Psychiatric Disorders

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Abstract

Executive functions (EFs) have been proposed as an endophenotype for psychopathology because EF deficits are associated with most psychiatric disorders. To examine this hypothesis, we derived polygenic risk scores for autism, attention-deficit/hyperactive disorder (ADHD), bipolar disorder, major depression (MDD), and schizophrenia, using genome-wide data from the Psychiatric Genomics Consortium as discovery samples. We then examined the relationships between these polygenic risk scores and three separable EF components measured with a latent variable model. We also examined the relationship between genetic risk for ADHD and MDD and their respective symptom counts and lifetime diagnoses. We found no evidence for larger effect sizes for EFs as endophenotypes for psychiatric disorders. However, larger sample sizes will be important in examining this relationship further.

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Notes

  1. Across all waves, only 4 scores were not computed because the participant did not answer at least 16 questions.

  2. Visual inspection involved comparing the self-reported ancestry to the places in the distribution that showed breakpoints (or drop-offs) between the sample's ancestry groups. This resulted in identification of European ancestry participants by component 1 > 0.014, 0 < component 2 < 0.013, and component 3 > -0.006.

  3. To include individuals without genetic data in the estimation of the EF latent variables (Mplus will exclude individuals missing on covariates) and other phenotypic measures, we imputed missing PCs as the average for that self-identified ethnicity in our genetic sample. The number of individuals who contributed to each phenotype was as follows: EFs = 1543; CES-D = 2875; CBCL = 1684; IQ = 1571; DIS diagnoses = 2875.

  4. This interaction term was included even though it was not significant in any models.

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Funding

This research was supported by National Institute of Health Grants MH063207, MH001865, MH016880, MH079485, DA011015, DA035804, AG046938, and HD010333.

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Authors and Affiliations

  1. Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA

    Chelsie E. Benca, Matthew C. Keller, John K. Hewitt & Naomi P. Friedman

  2. Department of Psychology, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL, USA

    Jaime L. Derringer

  3. Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA

    Chelsie E. Benca, Robin P. Corley, Matthew C. Keller, John K. Hewitt & Naomi P. Friedman

  4. Division of Substance Dependence, Psychiatry Department, University of Colorado Denver, Denver, CO, USA

    Susan E. Young

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  1. Chelsie E. Benca
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  2. Jaime L. Derringer
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Correspondence to Chelsie E. Benca.

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Chelsie E. Benca, Jaime L. Derringer, Robin P. Corley, Susan E. Young, Matthew C. Keller, John K. Hewitt, and Naomi P. Friedman declares that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of Colorado Institutional Review Board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Parental permission and informed consent or assent were obtained from each subject at each assessment.

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Benca, C.E., Derringer, J.L., Corley, R.P. et al. Predicting Cognitive Executive Functioning with Polygenic Risk Scores for Psychiatric Disorders. Behav Genet 47, 11–24 (2017). https://doi.org/10.1007/s10519-016-9814-2

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