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Polygenic risk and the course of attention-deficit/hyperactivity disorder from childhood to young adulthood: findings from a nationally-representative cohort

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Jessica Blais, Daniel Belsky, Avshalom Caspi, Andrea Danese, Terrie Moffitt, Guilherme Polanczyk, Karen Sugden, Jasmin Wertz, Ben Williams, Cathryn Lewis, Louise Arseneault

Original languageEnglish
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Accepted/In press31 Dec 2020

King's Authors


Objective: To understand whether genetic risk for attention-deficit hyperactivity disorder (ADHD) is associated with 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-report and at age 18 with self-report. Polygenic risk scores (PRS) 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: Individuals with higher ADHD PRS had increased risk for meeting ADHD diagnostic criteria (ORs 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 (IRR=1.18) and inattention (IRR=1.14) from age 5 to age 12. In young adulthood, persistent ADHD exhibited the highest PRS (mean PRS=0.37), followed by those with remission (mean=0.21); both had higher PRS than controls (mean=-0.03), but did not significantly differ from one another. 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 GWAS may have relevance for not only incidence of mental health disorders, but for understanding the longitudinal course of mental health problems.

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