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Meta-Analysis
, 51 (1), 63-75

Discovery of the First Genome-Wide Significant Risk Loci for Attention Deficit/Hyperactivity Disorder

Ditte Demontis  1   2   3 Raymond K Walters  4   5 Joanna Martin  5   6   7 Manuel Mattheisen  1   2   3   8   9   10 Thomas D Als  1   2   3 Esben Agerbo  1   11   12 Gísli Baldursson  13 Rich Belliveau  5 Jonas Bybjerg-Grauholm  1   14 Marie Bækvad-Hansen  1   14 Felecia Cerrato  5 Kimberly Chambert  5 Claire Churchhouse  4   5   15 Ashley Dumont  5 Nicholas Eriksson  16 Michael Gandal  17   18   19   20 Jacqueline I Goldstein  4   5   15 Katrina L Grasby  21 Jakob Grove  1   2   3   22 Olafur O Gudmundsson  13   23   24 Christine S Hansen  1   14   25 Mads Engel Hauberg  1   2   3 Mads V Hollegaard  1   14 Daniel P Howrigan  4   5 Hailiang Huang  4   5 Julian B Maller  5   26 Alicia R Martin  4   5   15 Nicholas G Martin  21 Jennifer Moran  5 Jonatan Pallesen  1   2   3 Duncan S Palmer  4   5 Carsten Bøcker Pedersen  1   11   12 Marianne Giørtz Pedersen  1   11   12 Timothy Poterba  4   5   15 Jesper Buchhave Poulsen  1   14 Stephan Ripke  4   5   27 Elise B Robinson  4   28 F Kyle Satterstrom  4   5   15 Hreinn Stefansson  23 Christine Stevens  5 Patrick Turley  4   5 G Bragi Walters  23   24 Hyejung Won  17   18 Margaret J Wright  29 ADHD Working Group of the Psychiatric Genomics Consortium (PGC)Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium23andMe Research TeamOle A Andreassen  30 Philip Asherson  31 Christie L Burton  32 Dorret I Boomsma  33   34 Bru Cormand  35   36   37   38 Søren Dalsgaard  11 Barbara Franke  39 Joel Gelernter  40   41 Daniel Geschwind  17   18   19 Hakon Hakonarson  42 Jan Haavik  43   44 Henry R Kranzler  45   46 Jonna Kuntsi  31 Kate Langley  7   47 Klaus-Peter Lesch  48   49   50 Christel Middeldorp  33   51   52 Andreas Reif  53 Luis Augusto Rohde  54   55 Panos Roussos  56   57   58   59 Russell Schachar  32 Pamela Sklar  56   57   58 Edmund J S Sonuga-Barke  60 Patrick F Sullivan  6   61 Anita Thapar  7 Joyce Y Tung  16 Irwin D Waldman  62 Sarah E Medland  21 Kari Stefansson  23   24 Merete Nordentoft  1   63 David M Hougaard  1   14 Thomas Werge  1   25   64 Ole Mors  1   65 Preben Bo Mortensen  1   2   11   12 Mark J Daly  4   5   15   66 Stephen V Faraone  67 Anders D Børglum  68   69   70 Benjamin M Neale  71   72   73
Collaborators, Affiliations
Meta-Analysis

Discovery of the First Genome-Wide Significant Risk Loci for Attention Deficit/Hyperactivity Disorder

Ditte Demontis et al. Nat Genet.

Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

Comment in

  • First genetic risk loci for ADHD identified.
    Ridler C. Ridler C. Nat Rev Neurol. 2019 Jan;15(1):4. doi: 10.1038/s41582-018-0117-5. Nat Rev Neurol. 2019. PMID: 30531819 No abstract available.
  • Risk loci for ADHD.
    Clyde D. Clyde D. Nat Rev Genet. 2019 Feb;20(2):69. doi: 10.1038/s41576-018-0084-0. Nat Rev Genet. 2019. PMID: 30532079 No abstract available.

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