Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Demontis, Ditte; Walters, G. Bragi; Athanasiadis, Georgios; Walters, Raymond K.; 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; Guðmundsson, Ólafur Ó.; Magnússon, Sigurður H.; Baldursson, Gísli; Davíðsdóttir, Katrín; Haraldsdóttir, Gyða S.; Agerbo, Esben; Hoffman, Gabriel E.; Dalsgaard, Søren; Martin, Joanna; Ribasès, Marta; Boomsma, Dorret I.; Artigas, María Soler; Mota, Nina Roth; Howrigan, Daniel P.; Medland, Sarah E.; Zayats, Tetyana; Rajagopal, Veera M.; Havdahl, Alexandra; Doyle, Alysa E.; Reif, Andreas; Thapar, Anita; Cormand, Bru; Liao, Calwing; Burton, Christie L.; Bau, Claiton H.D.; Rovaris, Diego Luiz; Sonuga‐Barke, Edmund; Corfield, Elizabeth C.; Grevet, Eugênio H.; Larsson, Henrik; Gizer, Ian R.; Waldman, Irwin D.; Brikell, Isabell; Haavik, Jan; Crosbie, Jennifer; McGough, James J.; Kuntsi, Jonna; Glessner, Joseph; Langley, K.; Lesch, Klaus‐Peter; Rohde, Luís Augusto; Hutz, Mara Helena; Klein, Marieke; Bellgrove, Mark A.; Tesli, Martin; O’Donovan, Michael; Andreassen, Ole A.; Leung, Patrick W. L.; Pan, Pedro Mário; Joober, Ridha; Schachar, Russell; Loo, Sandra K.; Witt, Stephanie H.; Reichborn‐Kjennerud, Ted; Banaschewski, Tobias; Hawi, Ziarih; Daly, Mark J.; Mors, Ole; Nordentoft, Merete; Mors, Ole; Hougaard, David M.; Mortensen, Preben Bo; Daly, Mark J.; Faraone, Stephen V.; Stefánsson, Hreinn; Roussos, Panos; Franke, Barbara; Werge, Thomas; Neale, Benjamin M.; Stefánsson, Kāri; Børglum, Anders D.

doi:10.1038/s41588-022-01285-8

reviewNature GeneticsJan 26, 2023GOLD OA

Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

DDDitte Demontis GBG. Bragi Walters GAGeorgios Athanasiadis RKRaymond K. Walters KTKaren Therrien

Aarhus University · Lundbeck Foundation · +66 more institutions

PubMed

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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…

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Keywords

Biology
Genetic architecture
Genome-wide association study
Computational biology
Cognition
Genetics
Genome
Evolutionary biology

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