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,Daniel W Belsky,Avshalom Caspi,Andrea Danese,Terrie E Moffitt,Guilherme V Polanczyk,Karen Sugden,Jasmin Wertz,Benjamin S Williams,Cathryn M Lewis,Louise Arseneault

doi:10.1016/j.jaac.2020.12.033

Abstract

ObjectiveTo understand whether genetic risk for attention-deficit/hyperactivity disorder (ADHD) is associated with the course of the disorder across childhood and into young adulthood.MethodParticipants 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.ResultsParticipants 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.ConclusionGenetic 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.

Highlights

Children with a higher attention-deficit/hyperactivity disorder (ADHD) Polygenic risk scores (PRSs) were at increased risk of meeting ADHD diagnostic criteria at ages 5, 7, 10, and 12 (Table 1)
At age 5, an increase of 1 SD in ADHD PRS was associated with a 45% increased risk of ADHD, and at age 12, a 1 SD increase was associated with a 54% increased risk
ADHD PRS was associated with number of times a participant met ADHD criteria across childhood: a 1 SD increase in PRS was associated with nearly twice the risk of meeting criteria at 3 or 4 childhood assessments

Summary

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. PRSs derived from GWASs are one way to capture genetic liability to ADHD These scores have been shown to explain about 5% of the variance of ADHD casecontrol status in independent samples[1] and are associated with dimensional measures of ADHD symptoms in both clinical and population-based studies.[11,12,13] less is known about how ADHD PRS is associated with the longitudinal course of the disorder and whether people with a high genetic burden, as reflected in higher PRSs, may be more likely to show a more persistent course. We investigated whether genetic risk for other mental health disorders commonly comorbid with ADHD (depression, alcohol dependence, and marijuana use disorder) were associated with ADHD course, either through contributing to persistence or influencing risk for late-onset ADHD

METHOD

RESULTS

DISCUSSION