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Title: Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains
Author: Demontis, Dittie
Walters, G. Bragi
Athanasiadis, Georgios
Walters, Raymond
Therrien, Karen
Farajzadeh, Leila
Voloudakis, Georgios
Bendl, Jaroslav
Zeng, Biau
Zhang, Wen
Grove, Jakob
Als, Thomas D.
Duan, Jinjie
Satterstrom, F.Kyle
Bybjerg Grauholm, Jonas
Bækved Hansen, Marie
Gudmundsson, Ofaur O.
Magnusson, Sigurdur H.
Baldursson, Gisli
Davidsdottir, Katrin
Haraldsdottir, Gyda S.
Nielsen, Trine Tollerup
Agerbo, Esben
Hoffman, Gabriel E.
Dalsgaard, S.
Martin, Joanna
Ribasés Haro, Marta
Boomsma, Dorret I.
Soler Artigas, Maria
Roth Mota, Nina
Howrigan, Daniel
Medland, Sarah E.
Zayats, Tetyana
ADHD Working Group of the Psychiatric Genomics Consortium
iPSYCH-Broad Consortium
Nordentoft, Merete
Mors, Ole
Hougaard, David M.
Mortensen, Preben Bo
Cormand, Bru
Keywords: Trastorns per dèficit d'atenció amb hiperactivitat en els adults
Attention deficit disorder with hyperactivity in adults
Issue Date: 26-Jan-2023
Publisher: Nature Publishing Group
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 impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.
Note: Versió postprint del document publicat a:
It is part of: Nature Genetics, 2023, vol. 55, p. 198-208
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ISSN: 1061-4036
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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