Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort

Abstract

Importance: Knowledge of the mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) symptoms can inform psychosocial interventions. Objective: To investigate whether parental genetic risk factors associate with their children s ADHD symptoms due to genetic transmission of risk or due to parental genetic liability that influences offspring ADHD via parenting environments (genetic nurture). Design and participants: This study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. This prospective cohort study consisted of 5,405 mother-father-offspring trios recruited between 1999 - 2008. Exposures: We calculated polygenic scores for parental traits previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment and intellectual ability. Main outcomes and measures: Mothers reported on their 8-year-old children s ADHD symptoms using the Parent/Teacher Rating Scale for Disruptive Behavior Disorders. Results: Maternal polygenic scores for ADHD, autism spectrum disorder (ASD), neuroticism and smoking predicted child ADHD symptoms in bivariate analyses. After jointly modelling maternal, paternal and child polygenic scores, ADHD symptoms were predicted by children s polygenic scores for ADHD ({beta} = 0.10; 95% CI 0.07 to 0.14), smoking ({beta} = 0.07; 95% CI 0.03 to 0.10) and educational attainment ({beta} = -0.09; 95% CI -0.13 to -0.05), indicating direct genetic transmission of risk. Mothers polygenic scores for ASD ({beta} = 0.05; 95% CI 0.02 to 0.08) and neuroticism ({beta} = 0.05; 95% CI 0.01 to 0.08) predicted children s ADHD symptoms conditional on fathers and children s scores, implicating genetic nurture, or effects due to population stratification or assortative mating. Conclusions: These results suggest that associations between some parental traits and offspring ADHD symptoms likely reflect a nuanced mix of direct genetic transmission (ADHD, smoking and educational attainment) and genetic nurture (ASD and neuroticism). If confirmed, these findings support previous evidence that maternal ASD or neuroticism may be possible targets for intervention to help break the chain of the intergenerational transmission of ADHD risk. Keywords: MoBa, attention-deficit/hyperactivity disorder, intergenerational transmission, genetic nurture, parenting.