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. 2021 Sep;60(9):1147-1156.
doi: 10.1016/j.jaac.2020.12.033. Epub 2021 Jan 10.

Polygenic Risk and the Course of Attention-Deficit/Hyperactivity Disorder From Childhood to Young Adulthood: Findings From a Nationally Representative Cohort

Jessica C Agnew-Blais  1 , Daniel W Belsky  2 , Avshalom Caspi  3 , Andrea Danese  4 , Terrie E Moffitt  3 , Guilherme V Polanczyk  5 , Karen Sugden  6 , Jasmin Wertz  6 , Benjamin S Williams  6 , Cathryn M Lewis  1 , Louise Arseneault  7
Affiliations

Polygenic Risk and the Course of Attention-Deficit/Hyperactivity Disorder From Childhood to Young Adulthood: Findings From a Nationally Representative Cohort

Jessica C Agnew-Blais et al. J Am Acad Child Adolesc Psychiatry. 2021 Sep.

Abstract

Objective: To understand whether genetic risk for attention-deficit/hyperactivity disorder (ADHD) is associated with the course of the disorder across childhood and into young adulthood.

Method: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2,232 twins. ADHD was assessed at ages 5, 7, 10, and 12 with mother- and teacher-reports and at age 18 with self-report. Polygenic risk scores (PRSs) were created using a genome-wide association study of ADHD case status. Associations with PRS were examined at multiple points in childhood and longitudinally from early childhood to adolescence. We investigated ADHD PRS and course to young adulthood, as reflected by ADHD remission, persistence, and late onset.

Results: Participants with higher ADHD PRSs had increased risk for meeting ADHD diagnostic criteria (odds ratios ranging from 1.17 at age 10 to 1.54 at age 12) and for elevated symptoms at ages 5, 7, 10, and 12. Higher PRS was longitudinally associated with more hyperactivity/impulsivity (incidence rate ratio = 1.18) and inattention (incidence rate ratio = 1.14) from age 5 to age 12. In young adulthood, participants with persistent ADHD exhibited the highest PRS (mean PRS = 0.37), followed by participants with remission (mean PRS = 0.21); both groups had higher PRS than controls (mean PRS = -0.03), but did not significantly differ from one another. Participants with late-onset ADHD did not show elevated PRS for ADHD, depression, alcohol dependence, or marijuana use disorder.

Conclusion: Genetic risk scores derived from case-control genome-wide association studies may have relevance not only for incidence of mental health disorders, but also for understanding the longitudinal course of mental health disorders.

Keywords: ADHD; development; longitudinal; polygenic risk score.

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Figures

Figure 1
Figure 1
Attention-Deficit/Hyperactivity Disorder (ADHD) Course to Young Adulthood (Remission, Persistence, and Late-Onset) and ADHD Polygenic Risk Note:PRS = Polygenic risk score. Please note color figures are available online.
Figure 2
Figure 2
Polygenic Risk for Depression, Alcohol Dependence, and Marijuana Use Disorder and Course of Attention-Deficit/Hyperactivity Disorder (ADHD) (Remission, Persistence, and Late-Onset) at Age 18 Note:Polygenic risk scores (PRSs) for (a) major depressive disorder (MDD), (b) alcohol dependence, and (c) marijuana use disorder. Please note color figures are available online.
See this image and copyright information in PMC

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