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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

https://doi.org/10.1016/j.jaac.2020.12.033Get rights and content
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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.

Key words

ADHD
development
longitudinal
polygenic risk score

Cited by (0)

The Environmental Risk (E-Risk) Longitudinal Twin Study is funded by the United Kingdom Medical Research Council (UKMRC grant G1002190). Additional support was provided by the U.S. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) grant HD077482 and by the Jacobs Foundation. Jessica Agnew-Blais is an MRC Skills Development Fellow. Louise Arseneault is the Mental Health Leadership Fellow for the United Kingdom Economic and Social Research Council (ESRC). Daniel W. Belsky is a fellow of the Canadian Institute for Advanced Research Child Brain Development Network. Jasmin Wertz is supported by a postdoctoral fellowship from the AXA Research Fund. Cathryn M. Lewis is partially funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

Author Contributions

Conceptualization: Agnew-Blais, Belsky, Caspi, Danese, Moffitt, Lewis, Polanczyk, Wertz, Arseneault

Data curation: Agnew-Blais

Formal analysis: Agnew-Blais, Sugden

Funding acquisition: Moffitt, Arseneault, Caspi

Investigation: Agnew-Blais, Moffitt, Arseneault, Caspi

Methodology: Agnew-Blais, Belsky, Caspi, Sugden, Williams, Lewis, Arseneault

Supervision: Lewis, Arseneault

Writing – original draft: Agnew-Blais

Writing – review and editing: Agnew-Blais, Belsky, Caspi, Danese, Moffitt, Polanczyk, Sugden, Wertz, Williams, Lewis, Arseneault

The authors are grateful to the study members and their families for their participation. They thank CACI Inc. and members of the E-Risk team for their dedication, hard work, and insights.

Disclosure: Drs. Agnew-Blais, Belsky, Caspi, Danese, Moffitt, Polanczyk, Sugden, Wertz, Lewis, and Arseneault and Mr. Williams have reported no biomedical financial interests or potential conflicts of interest.