Impact of Polygenic versus Environmental Risk Factors on ADHD Diagnosis among School Aged Children in the ABCD Study

Keiko Kunitoki, MD, MPH

Massachusetts General Hospital – Fellow
KUNITOKI_KEIKO poster

Scientific Abstract

Background: Risk for ADHD is associated with both genetic and environmental factors, but the relative burden of these classes of risk remains uncertain.  We sought to determine attributable risk estimates for known genetic and environmental risk factors in a large study of youth age 9-10.

Methods: Using baseline data from 3,390 children participating in the Adolescent Brain Cognitive Development (ABCD) Study, we extracted Child Behavior Checklist​ (CBCL) total and attention score, ADHD diagnosis (past, present, unspecified) from the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), along with a total of 13 environmental exposures selected a priori based on the ADHD literature:  low neighborhood safety, economic hardship, screen time, extracurricular activities, divorce, unplanned pregnancy, c-section, drug abuse, pregnancy or birth complications. Among participants with European ancestry, ADHD polygenic risk score (PRS) was calculated based on Psychiatric Genomics Consortium (PGC) summary statistics. First, we tested the accuracy of predicting ADHD onset by age 9-10 with ROC analysis. Then, we calculated relative risk and population attributable fraction (PAF) for each risk factor, along with estimated weighted overall PAF accounting for overlapping variance principal component analysis. 

Results: Prevalence of all ADHD among this cohort was 19.2%. ADHD PRS has poor predictivity of ADHD diagnosis by age 9-10 (AUC: 0.550, 95%CI 0.528-0.571). Weighted overall PAF for ADHD diagnosis was 0.38.  Weighted PAF across environmental factors 0.32, compared to 0.038 for ADHD polygenic risk. 

Conclusions:  Common environmental exposures cumulatively associate with substantial greater risk for ADHD diagnosis at age 9-10 compared to that attributable to genetic loading, as presently indexed.  While correlational, these findings may be verified in fully prospective studies, such as the planned Healthy Brain and Child Development (HBCD) Study.  As several of these environmental factors are potentially modifiable, these findings suggest the possibility of prevention in some cases of ADHD.

Live Zoom Session – March 9th

research Areas

Authors

Keiko Kunitoki, MD, MPH, Dylan Hughes, Alysa Doyle, PhD, Joshua L. Roffman, MD, MMSc

Principal Investigator

Joshua L. Roffman, MD, MMSc