Risk Variants and Polygenic Architecture of Disruptive Behavior Disorders in the Context of Attention-deficit/hyperactivity Disorder

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 26

PMID 33495439

Citations 13

Authors

Ditte Demontis

Raymond K Walters

Veera M Rajagopal

Irwin D Waldman

Jakob Grove

Thomas D Als

Soren Dalsgaard

Marta Ribases

Jonas Bybjerg-Grauholm

Maria Baekvad-Hansen

Thomas Werge

Merete Nordentoft

Ole Mors

Preben Bo Mortensen

Bru Cormand

David M Hougaard

Benjamin M Neale

Barbara Franke

Stephen V Faraone

Anders D Borglum

Affiliations

Soon will be listed here.

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h = 0.34) when compared to ADHD without DBDs (h = 0.20), high genetic correlations between ADHD + DBDs and aggressive (r = 0.81) and anti-social behaviors (r = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

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