Genetic markers of ADHD-related variations in intracranial volume

Marieke Klein; Raymond Kenney Walters; Ditte Demontis; Jason L. Stein; Derrek P. Hibar; Hieab H.H. Adams; Janita Bralten; Nina Roth Mota; Russell James Schachar; Edmund J. S. Sonuga-Barke; Manuel Mattheisen; Benjamin M. Neale; Paul M. Thompson; Sarah Elizabeth Medland; Anders Dupont Børglum; Stephen V. Faraone; Alejandro Arias Vásquez; Barbara Franke

doi:10.1176/appi.ajp.2018.18020149

GeneticsAmerican Journal of PsychiatryMar 1, 2019

Peer-reviewed journal article

Genetic markers of ADHD-related variations in intracranial volume

Marieke Klein iD, Raymond Kenney Walters iD, Ditte Demontis iD, Jason L. Stein iD, Derrek P. Hibar iD, Hieab H.H. Adams iD, Janita Bralten iD, Nina Roth Mota iD, Russell James Schachar iD, Edmund J. S. Sonuga-Barke iD, Manuel Mattheisen iD, Benjamin M. Neale iD, Paul M. Thompson iD, Sarah Elizabeth Medland iD, Anders Dupont Børglum iD, Stephen V. Faraone iD, Alejandro Arias Vásquez iD, Barbara Franke iD

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex pathophysiology, where genetic risk is hypothesized to be mediated by alterations in structure and function of diverse brain networks. We tested one aspect of this hypothesis by investigating the genetic overlap between ADHD (n=55,374) and (mainly subcortical) brain volumes (n=11,221-24,704), using the largest publicly available studies. At the level of common variant genetic architecture, we discovered a significant negative genetic correlation between ADHD and intracranial volume (ICV). Meta-analysis of individual variants found significant loci associated with both ADHD risk and ICV; additional loci were identified for ADHD and amygdala, caudate nucleus, and putamen volumes. Gene-set analysis in the ADHD-ICV meta-analytic data showed significant association with variation in neurite outgrowth-related genes. In summary, our results suggest new hypotheses about biological mechanisms involved in ADHD etiology and highlight the need to study additional brain parameters.

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