Produção Nacional
Revisado por pares
Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains
2023; Nature Portfolio; Volume: 55; Issue: 2 Linguagem: Inglês
10.1038/s41588-022-01285-8
ISSN1546-1718
AutoresDitte Demontis, G. Bragi Walters, Georgios Athanasiadis, Raymond K. Walters, Karen Therrien, Trine Tollerup Nielsen, Leila Farajzadeh, Georgios Voloudakis, Jaroslav Bendl, Biau Zeng, Wen Zhang, Jakob Grove, Thomas D. Als, Jinjie Duan, F. Kyle Satterstrom, Jonas Bybjerg‐Grauholm, Marie Bækved-Hansen, Ólafur Ó. Guðmundsson, Sigurður H. Magnússon, Gísli Baldursson, Katrín Davíðsdóttir, Gyða S. Haraldsdóttir, Esben Agerbo, Gabriel E. Hoffman, Søren Dalsgaard, Joanna Martin, Marta Ribasés, Dorret I. Boomsma, María Soler Artigas, Nina Roth Mota, Daniel P. Howrigan, Sarah E. Medland, Tetyana Zayats, Veera M. Rajagopal, Alexandra Havdahl, Alysa E. Doyle, Andreas Reif, Anita Thapar, Bru Cormand, Calwing Liao, Christie L. Burton, Claiton H.D. Bau, Diego Luiz Rovaris, Edmund Sonuga‐Barke, Elizabeth C. Corfield, Eugênio H. Grevet, Henrik Larsson, Ian R. Gizer, Irwin D. Waldman, Isabell Brikell, Jan Haavik, Jennifer Crosbie, James J. McGough, Jonna Kuntsi, Joseph Glessner, K. Langley, Klaus‐Peter Lesch, Luís Augusto Rohde, Mara Helena Hutz, Marieke Klein, Mark A. Bellgrove, Martin Tesli, Michael O’Donovan, Ole A. Andreassen, Patrick W. L. Leung, Pedro Mário Pan, Ridha Joober, Russell Schachar, Sandra K. Loo, Stephanie H. Witt, Ted Reichborn‐Kjennerud, Tobias Banaschewski, Ziarih Hawi, Mark J. Daly, Ole Mors, Merete Nordentoft, Ole Mors, David M. Hougaard, Preben Bo Mortensen, Mark J. Daly, Stephen V. Faraone, Hreinn Stefánsson, Panos Roussos, Barbara Franke, Thomas Werge, Benjamin M. Neale, Kāri Stefánsson, Anders D. Børglum,
Tópico(s)Attention Deficit Hyperactivity Disorder
ResumoAttention-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. Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.
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