Abstract

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impai...

Authors	Demontis, D; Walters, GB; Athanasiadis, G; Walters, R; Therrien, K; Nielsen, TT; Farajzadeh, L; Voloudakis, G; Bendl, J; Zeng, B; Zhang, W; Grove, J; Als, TD; Duan, J; Satterstrom, FK; Bybjerg-Grauholm, J; Bækved-Hansen, M; Gudmundsson, OO; Magnusson, SH; Baldursson, G; Davidsdottir, K; Haraldsdottir, GS; Agerbo, E; Hoffman, GE; Dalsgaard, S; Martin, J; Ribasés, M; Boomsma, DI; Soler Artigas, M; Roth Mota, N; Howrigan, D; Medland, SE; Zayats, T; Rajagopal, VM; ADHD Working Group of the Psychiatric Genomics Consortium; iPSYCH-Broad Consortium; Nordentoft, M; Mors, O; Hougaard, DM; Mortensen, PB; Daly, MJ; Faraone, SV; Stefansson, H; Roussos, P; Franke, B; Werge, T; Neale, BM; Stefansson, K; Børglum, AD
Journal	NATURE GENETICS
Pages	198-208
Volume	55
Date	26/02/2023
Grant ID	R01 MH124851 | NIMH NIH HHS [MH] (United States); U01 MH116442 | NIMH NIH HHS [MH] (United States); R37 MH107649 | NIMH NIH HHS [MH] (United States); MR/L010305/1 | Medical Research Council [MRC_] (United Kingdom); S10 OD026880 | NIH HHS [OD] (United States); T32 MH087004 | NIMH NIH HHS [MH] (United States); U01 MH109514 | NIMH NIH HHS [MH] (United States); S10 OD030463 | NIH HHS [OD] (United States); R01 MH125246 | NIMH NIH HHS [MH] (United States); K08 MH122911 | NIMH NIH HHS [MH] (United States)
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41588-022-01285-8