학술논문
Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains
Document Type
Article
Author
Demontis, Ditte; Walters, G. Bragi; Athanasiadis, Georgios; Walters, Raymond; Therrien, Karen; Nielsen, Trine Tollerup; 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, Olafur O.; Magnusson, Sigurdur H.; Baldursson, Gisli; Davidsdottir, Katrin; Haraldsdottir, Gyda S.; Agerbo, Esben; Hoffman, Gabriel E.; Dalsgaard, Søren; Martin, Joanna; Ribasés, Marta; Boomsma, Dorret I.; Soler Artigas, Maria; Roth Mota, Nina; Howrigan, Daniel; Medland, Sarah E.; Zayats, Tetyana; Rajagopal, Veera M.; Nordentoft, Merete; Mors, Ole; Hougaard, David M.; Mortensen, Preben Bo; Daly, Mark J.; Faraone, Stephen V.; Stefansson, Hreinn; Roussos, Panos; Franke, Barbara; Werge, Thomas; Neale, Benjamin M.; Stefansson, Kari; Børglum, Anders D.
Source
Nature Genetics; 20230101, Issue: Preprints p1-11, 11p
Subject
Language
ISSN
10614036; 15461718
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 SORCS3in 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.