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

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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; 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.; Havdahl, Alexandra; Doyle, Alysa; Reif, Andreas; Thapar, Anita; Cormand, Bru; Liao, Calwing; Burton, Christie; Bau, Claiton H.D.; Rovaris, Diego Luiz; Sonuga-Barke, Edmund; Corfield, Elizabeth; Grevet, Eugenio Horacio; Larsson, Henrik; Gizer, Ian R.; Nordentoft, Merete; Werge, Thomas; ADHD Working Group of the Psychiatric Genomics Consortium; iPSYCH-Broad Consortium.

I: Nature Genetics, Bind 55, 2023, s. 198–208.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

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, Havdahl, A, Doyle, A, Reif, A, Thapar, A, Cormand, B, Liao, C, Burton, C, Bau, CHD, Rovaris, DL, Sonuga-Barke, E, Corfield, E, Grevet, EH, Larsson, H, Gizer, IR, Nordentoft, M, Werge, T, ADHD Working Group of the Psychiatric Genomics Consortium & iPSYCH-Broad Consortium 2023, 'Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains', Nature Genetics, bind 55, s. 198–208. https://doi.org/10.1038/s41588-022-01285-8

APA

Demontis, D., Walters, G. B., Athanasiadis, G., Walters, R., Therrien, K., Nielsen, T. T., Farajzadeh, L., Voloudakis, G., Bendl, J., Zeng, B., Zhang, W., Grove, J., Als, T. D., Duan, J., Satterstrom, F. K., Bybjerg-Grauholm, J., Bækved-Hansen, M., Gudmundsson, O. O., Magnusson, S. H., ... iPSYCH-Broad Consortium (2023). Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Nature Genetics, 55, 198–208. https://doi.org/10.1038/s41588-022-01285-8

Vancouver

Demontis D, Walters GB, Athanasiadis G, Walters R, Therrien K, Nielsen TT o.a. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Nature Genetics. 2023;55:198–208. https://doi.org/10.1038/s41588-022-01285-8

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. ; Havdahl, Alexandra ; Doyle, Alysa ; Reif, Andreas ; Thapar, Anita ; Cormand, Bru ; Liao, Calwing ; Burton, Christie ; Bau, Claiton H.D. ; Rovaris, Diego Luiz ; Sonuga-Barke, Edmund ; Corfield, Elizabeth ; Grevet, Eugenio Horacio ; Larsson, Henrik ; Gizer, Ian R. ; Nordentoft, Merete ; Werge, Thomas ; ADHD Working Group of the Psychiatric Genomics Consortium ; iPSYCH-Broad Consortium. / Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. I: Nature Genetics. 2023 ; Bind 55. s. 198–208.

Bibtex

@article{4e97603e8b6b4a60b607130cdf782191,
title = "Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains",
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.",
author = "Ditte Demontis and Walters, {G. Bragi} and Georgios Athanasiadis and Raymond Walters and Karen Therrien and Nielsen, {Trine Tollerup} and Leila Farajzadeh and Georgios Voloudakis and Jaroslav Bendl and Biau Zeng and Wen Zhang and Jakob Grove and Als, {Thomas D.} and Jinjie Duan and Satterstrom, {F. Kyle} and Jonas Bybjerg-Grauholm and Marie B{\ae}kved-Hansen and Gudmundsson, {Olafur O.} and Magnusson, {Sigurdur H.} and Gisli Baldursson and Katrin Davidsdottir and Haraldsdottir, {Gyda S.} and Esben Agerbo and Hoffman, {Gabriel E.} and S{\o}ren Dalsgaard and Joanna Martin and Marta Ribas{\'e}s and Boomsma, {Dorret I.} and {Soler Artigas}, Maria and {Roth Mota}, Nina and Daniel Howrigan and Medland, {Sarah E.} and Tetyana Zayats and Rajagopal, {Veera M.} and Alexandra Havdahl and Alysa Doyle and Andreas Reif and Anita Thapar and Bru Cormand and Calwing Liao and Christie Burton and Bau, {Claiton H.D.} and Rovaris, {Diego Luiz} and Edmund Sonuga-Barke and Elizabeth Corfield and Grevet, {Eugenio Horacio} and Henrik Larsson and Gizer, {Ian R.} and Merete Nordentoft and Thomas Werge and {ADHD Working Group of the Psychiatric Genomics Consortium} and {iPSYCH-Broad Consortium}",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2023",
doi = "10.1038/s41588-022-01285-8",
language = "English",
volume = "55",
pages = "198–208",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

AU - Demontis, Ditte

AU - Walters, G. Bragi

AU - Athanasiadis, Georgios

AU - Walters, Raymond

AU - Therrien, Karen

AU - Nielsen, Trine Tollerup

AU - Farajzadeh, Leila

AU - Voloudakis, Georgios

AU - Bendl, Jaroslav

AU - Zeng, Biau

AU - Zhang, Wen

AU - Grove, Jakob

AU - Als, Thomas D.

AU - Duan, Jinjie

AU - Satterstrom, F. Kyle

AU - Bybjerg-Grauholm, Jonas

AU - Bækved-Hansen, Marie

AU - Gudmundsson, Olafur O.

AU - Magnusson, Sigurdur H.

AU - Baldursson, Gisli

AU - Davidsdottir, Katrin

AU - Haraldsdottir, Gyda S.

AU - Agerbo, Esben

AU - Hoffman, Gabriel E.

AU - Dalsgaard, Søren

AU - Martin, Joanna

AU - Ribasés, Marta

AU - Boomsma, Dorret I.

AU - Soler Artigas, Maria

AU - Roth Mota, Nina

AU - Howrigan, Daniel

AU - Medland, Sarah E.

AU - Zayats, Tetyana

AU - Rajagopal, Veera M.

AU - Havdahl, Alexandra

AU - Doyle, Alysa

AU - Reif, Andreas

AU - Thapar, Anita

AU - Cormand, Bru

AU - Liao, Calwing

AU - Burton, Christie

AU - Bau, Claiton H.D.

AU - Rovaris, Diego Luiz

AU - Sonuga-Barke, Edmund

AU - Corfield, Elizabeth

AU - Grevet, Eugenio Horacio

AU - Larsson, Henrik

AU - Gizer, Ian R.

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - ADHD Working Group of the Psychiatric Genomics Consortium

AU - iPSYCH-Broad Consortium

N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-022-01285-8

DO - 10.1038/s41588-022-01285-8

M3 - Journal article

C2 - 36702997

AN - SCOPUS:85146989048

VL - 55

SP - 198

EP - 208

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -

ID: 335666155