The predictive capacity of psychiatric and psychological polygenic risk scores for distinguishing cases in a child and adolescent psychiatric sample from controls

Arija G. Jansen*, Philip R. Jansen, Jeanne E. Savage, Julia Kraft, Nora Skarabis, Tinca J.C. Polderman, Gwen C. Dieleman

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: Psychiatric traits are heritable, highly comorbid and genetically correlated, suggesting that genetic effects that are shared across disorders are at play. The aim of the present study is to quantify the predictive capacity of common genetic variation of a variety of traits, as captured by their PRS, to predict case-control status in a child and adolescent psychiatric sample including controls to reveal which traits contribute to the shared genetic risk across disorders. Method: Polygenic risk scores (PRS) of 14 traits were used as predictor phenotypes to predict case-control status in a clinical sample. Clinical cases (N = 1,402), age 1–21, diagnostic categories: Autism spectrum disorders (N = 492), Attention-deficit/ hyperactivity disorders (N = 471), Anxiety (N = 293), disruptive behaviors (N = 101), eating disorders (N = 97), OCD (N = 43), Tic disorder (N = 50), Disorder of infancy, childhood or adolescence NOS (N = 65), depression (N = 64), motor, learning and communication disorders (N = 59), Anorexia Nervosa (N = 48), somatoform disorders (N = 47), Trauma/stress (N = 39) and controls (N = 1,448, age 17–84) of European ancestry. First, these 14 PRS were tested in univariate regression analyses. The traits that significantly predicted case-control status were included in a multivariable regression model to investigate the gain in explained variance when leveraging the genetic effects of multiple traits simultaneously. Results: In the univariate analyses, we observed significant associations between clinical status and the PRS of educational attainment (EA), smoking initiation (SI), intelligence, neuroticism, alcohol dependence, ADHD, major depression and anti-social behavior. EA (p-value: 3.53E-20, explained variance: 3.99%, OR: 0.66), and SI (p-value: 4.77E-10, explained variance: 1.91%, OR: 1.33) were the most predictive traits. In the multivariable analysis with these eight significant traits, EA and SI, remained significant predictors. The explained variance of the PRS in the model with these eight traits combined was 5.9%. Conclusion: Our study provides more insights into the genetic signal that is shared between childhood and adolescent psychiatric disorders. As such, our findings might guide future studies on psychiatric comorbidity and offer insights into shared etiology between psychiatric disorders. The increase in explained variance when leveraging the genetic signal of different predictor traits supports a multivariable approach to optimize precision accuracy for general psychopathology.

Original languageEnglish
Pages (from-to)1079-1089
Number of pages11
JournalJournal of Child Psychology and Psychiatry and Allied Disciplines
Volume62
Issue number9
DOIs
Publication statusPublished - Sep 2021

Bibliographical note

Funding Information:
The authors thank the participants of the Inside‐out, NESCOG, and Berlin Psychosis Study sample. The authors gratefully acknowledge financial support by the Sophia Stichting voor Wetenschappelijk Onderzoek (SSWO, grant number 593 and S14‐27). The funding organizations had no role in any of the following: the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The authors thank Danielle Posthuma and Frank Verhulst for their valuable contributions in study design, data collection and reviewing the manuscript. The authors thank Mark Patrick Roeling for the Inside‐out data collection. The manuscript is original, and not published, nor under concurrent consideration elsewhere. The authors have declared that they have no competing or potential conflicts of interest. Key points

Publisher Copyright:
© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • comorbidity
  • general P factor
  • Genetics
  • neurodevelopmental disorders
  • psychiatry

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