Objective: Attention deficit hyperactivity disorder (ADHD) is a Results: ADHD PRS was associated with 12 of 24 risk factors multifactorial neurodevelopmental disorder, yet the interplay (odds ratio range, 1.03–1.30), namely, small gestational age, between ADHD polygenic risk scores (PRSs) and other risk infections, traumatic brain injury, and most psychosocial risk factors remains relatively unexplored. The authors investifactors. Nineteen risk factors were associated with ADHD digated associations, confounding, and interactions of ADHD agnosis (odds ratio range, 1.20–3.68), and adjusting for ADHD PRS with birth-related, somatic, and psychosocial factors PRS and parental psychiatric history led to only minor attenpreviously associated with ADHD. uations. Only the interaction between ADHD PRS and maternal autoimmune disease survived correction for multiple testing. Methods: Participants included a random general population sample (N521,578) and individuals diagnosed with ADHD Conclusions: Higher ADHD PRS in the general population is (N513,697) from the genotyped Danish iPSYCH2012 case associated with small increases in risk for certain birth-related cohort, born between 1981 and 2005. The authors derived and somatic ADHD risk factors, and broadly to psychosocial ADHD PRSs and identified 24 factors previously associated adversity. Evidence of gene-environment interaction was with ADHD using national registers. Logistic regression was limited, as was confounding by ADHD PRS and family psyused to estimate associations of ADHD PRS with each risk chiatric history on ADHD risk factor associations. This suggests factor in the general population. Cox models were used to that the majority of the investigated ADHD risk factors act largely evaluate confounding of risk factor associations with ADHD independently of current ADHD PRS to increase risk of ADHD. diagnosis by ADHD PRS and parental psychiatric history, and interactions between ADHD PRS and each risk factor. Am J Psychiatry 2023; 180:73–88; doi: 10.1176/appi.ajp.21111105

Original languageEnglish
JournalThe American Journal of Psychiatry (Spanish Edition)
Pages (from-to)73-88
Number of pages16
Publication statusPublished - Jan 2023


  • Attention Deficit Hyperactivity Disorder (ADHD)
  • Environmental Risk Factors
  • Genetics/Genomics
  • Neurodevelopmental Disorders


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