Gene copy number variation and pediatric mental health/neurodevelopment in a general population
Mehdi Zarrei, Christie L. Burton, Worrawat Engchuan, Edward J. Higginbotham, John Wei, Sabah Shaikh, Nicole M. Roslin, Jeffrey R. MacDonald, Giovanna Pellecchia, Thomas Nalpathamkalam, Sylvia Lamoureux, Roozbeh Manshaei, Jennifer Howe, Brett Trost, Bhooma Thiruvahindrapuram, Christian R. Marshall, Ryan K. C. Yuen, Richard F. Wintle, Lisa J. Strug, Dimitri J. Stavropoulos, Jacob Vorstman, Paul Arnold, Daniele Merico, Marc Woodbury‐Smith, Jennifer Crosbie, Russell Schachar, Stephen W. Scherer
Abstract
We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health and cognition in a community sample of 7100 unrelated children and youth of European or East Asian ancestry (Spit for Science). Clinically significant or susceptibility CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of attention-deficit/hyperactivity disorder (ADHD) traits (P = 5.0 × 10-3), longer response inhibition (a cognitive deficit found in several mental health and neurodevelopmental disorders; P = 1.0 × 10-2) and increased prevalence of mental health diagnoses (P = 1.9 × 10-6, odds ratio: 3.09), specifically ADHD, autism spectrum disorder anxiety and learning problems/learning disorder (P's < 0.01). There was an increased burden of rare deletions in gene-sets related to brain function or expression in brain associated with more ADHD traits. With the current mental health crisis, our data established a baseline for delineating genetic contributors in pediatric-onset conditions.