Exploring the Behavioral and Emotional Manifestation of Polygenic Risk for Psychiatric Disorders Among Schoolchildren

Abstract

Objective: We examined the relationships between polygenic risk scores (PRS) for psychiatric disorders and behavioral and emotional problems. In addition, we explored whether these associations differed by sex and conducted mutually adjusted models to elucidate whether different PRS independently contributed to the same outcome.

Method: Participants included 4,709 individuals 5 to 18 years of age from the Spanish population-based INSchool cohort (mean age = 10.0 years; SD = 3.0, 45% female). PRS for attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, depression, schizophrenia, and anxiety were computed using PRScs and PLINK. Behavioral and emotional problems were assessed using the Child Behavior Checklist (CBCL), the Teacher's Report Form (TRF), the Youth Self-Report (YSR), and the Strengths and Difficulties Questionnaire (SDQ) reported by parents, teachers, and participants. Associations between PRS and behavioral and emotional problems were examined using linear mixed-effects models.

Results: Of a total of 54 traits, 35 showed significant associations that survived multiple testing correction (p < 1.54E-04) with at least one PRS for ADHD, ASD, and depression. PRS-ADHD showed the strongest associations with a wide range of behavioral and emotional problems reported by all 3 informants, which was shown to be largely independent of the effects of PRS-ASD and depression. Sex-stratified results revealed certain sex-specific associations, with the PRS-Schizophrenia showing stronger effects among boys compared to girls in parent-reported outcomes.

Conclusion: Polygenic risk for ADHD and, to a lesser extent, ASD and depression contributed to the expression of behavior and emotional problems among schoolchildren in a transdiagnostic manner, with both broad and specific measures of dimensional psychopathology.

Diversity & inclusion statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science.

Keywords: ADHD; polygenic scores; psychiatric disorders; schoolchildren.