Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
Ditte Demontis, Raymond K. Walters, Veera M. Rajagopal, Irwin D. Waldman, Jakob Grove, Thomas D. Als, Søren Dalsgaard, Marta Ribasés, Jonas Bybjerg‐Grauholm, Maria Bækvad-Hansen, Thomas Werge, Merete Nordentoft, Ole Mors, Preben Bo Mortensen, Ole A. Andreassen, María J. Arranz, Tobias Banaschewski, Claiton H.D. Bau, Mark A. Bellgrove, Joseph Biederman, Isabell Brikell, Jan K. Buitelaar, Christie L. Burton, Miguel Casas, Jennifer Crosbie, Alysa E. Doyle, Richard P. Ebstein, Josephine Elia, Elizabeth C. Corfield, Eugênio H. Grevet, Natalie Grizenko, Alexandra Havdahl, Ziarih Hawi, Johannes Hebebrand, Amaia Hervás, Sarah Hohmann, Jan Haavik, Ridha Joober, Lindsey Kent, Jonna Kuntsi, K. Langley, Henrik Larsson, Klaus‐Peter Lesch, Patrick W. L. Leung, Calwing Liao, Sandra K. Loo, Joanna Martin, Nicholas G. Martin, Sarah E. Medland, Ana Miranda, Nina Roth Mota, Robert D. Oades, Josep Antoni Ramos‐Quiroga, Andreas Reif, Marcella Rietschel, Herbert Roeyers, Luís Augusto Rohde, Aribert Rothenberger, Paula Rovira, Cristina Sánchez‐Mora, Russell Schachar, Sarojini M. Sengupta, María Soler Artigas, Hans‐Christoph Steinhausen, Anita Thapar, Stephanie H. Witt, Li Yang, Tetyana Zayats, Yanli Zhang‐James, Bru Cormand, David M. Hougaard, Benjamin M. Neale, Barbara Franke, Stephen V. Faraone, Anders D. Børglum
Abstract
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 −10 , OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h 2 SNP = 0.34) when compared to ADHD without DBDs (h 2 SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (r g = 0.81) and anti-social behaviors (r g = 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.