Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30478444
TITLE
Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.
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.
DATE PUBLISHED
2019 01
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/06/13
accepted 2018/09/28
pubmed 2018/11/28 06:00
medline 2019/04/25 06:00
entrez 2018/11/28 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Demontis D Demontis Ditte D Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
Walters RK Walters Raymond K RK Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Martin J Martin Joanna J MRC Centre for Neuropsychiatric Genetics & Genomics, School of Medicine, Cardiff University, Cardiff, UK.
Mattheisen M Mattheisen Manuel M Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
Als TD Als Thomas D TD Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
Agerbo E Agerbo Esben E Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
Baldursson G Baldursson Gísli G Department of Child and Adolescent Psychiatry, National University Hospital, Reykjavik, Iceland.
Belliveau R Belliveau Rich R Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Bybjerg-Grauholm J Bybjerg-Grauholm Jonas J Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Bækvad-Hansen M Bækvad-Hansen Marie M Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Cerrato F Cerrato Felecia F Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Chambert K Chambert Kimberly K Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Churchhouse C Churchhouse Claire C Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Dumont A Dumont Ashley A Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eriksson N Eriksson Nicholas N 23andMe, Inc, Mountain View, CA, USA.
Gandal M Gandal Michael M Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
Goldstein JI Goldstein Jacqueline I JI Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Grasby KL Grasby Katrina L KL QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Grove J Grove Jakob J Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
Gudmundsson OO Gudmundsson Olafur O OO Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Hansen CS Hansen Christine S CS Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Hauberg ME Hauberg Mads Engel ME Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
Hollegaard MV Hollegaard Mads V MV Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Howrigan DP Howrigan Daniel P DP Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Huang H Huang Hailiang H Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Maller JB Maller Julian B JB Genomics plc, Oxford, UK.
Martin AR Martin Alicia R AR Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Moran J Moran Jennifer J Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pallesen J Pallesen Jonatan J Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
Palmer DS Palmer Duncan S DS Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pedersen CB Pedersen Carsten Bøcker CB Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
Pedersen MG Pedersen Marianne Giørtz MG Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
Poterba T Poterba Timothy T Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Poulsen JB Poulsen Jesper Buchhave JB Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Ripke S Ripke Stephan S Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Robinson EB Robinson Elise B EB Department of Epidemiology, Harvard Chan School of Public Health, Boston, MA, USA.
Satterstrom FK Satterstrom F Kyle FK Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stefansson H Stefansson Hreinn H deCODE genetics/Amgen, Reykjavík, Iceland.
Stevens C Stevens Christine C Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Turley P Turley Patrick P Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Walters GB Walters G Bragi GB Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Won H Won Hyejung H Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
Wright MJ Wright Margaret J MJ Queensland Brain Institute, University of Queensland, Brisbane, Australia.
ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium
23andMe Research Team
Andreassen OA Andreassen Ole A OA NORMENT KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway.
Asherson P Asherson Philip P Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Burton CL Burton Christie L CL Psychiatry, Neurosciences and Mental Health, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Boomsma DI Boomsma Dorret I DI EMGO Institute for Health and Care Research, Amsterdam, The Netherlands.
Cormand B Cormand Bru B Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Barcelona, Catalonia, Spain.
Dalsgaard S Dalsgaard Søren S National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
Franke B Franke Barbara B Departments of Human Genetics (855) and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.
Gelernter J Gelernter Joel J Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Geschwind D Geschwind Daniel D Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Hakonarson H Hakonarson Hakon H The Center for Applied Genomics, The Children´s Hospital of Philadelphia, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Haavik J Haavik Jan J Haukeland University Hospital, Bergen, Norway.
Kranzler HR Kranzler Henry R HR Veterans Integrated Service Network (VISN4) Mental Illness Research, Education, and Clinical Center (MIRECC), Crescenz VA Medical Center, Philadephia, PA, USA.
Kuntsi J Kuntsi Jonna J Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Langley K Langley Kate K School of Psychology, Cardiff University, Cardiff, UK.
Lesch KP Lesch Klaus-Peter KP Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Middeldorp C Middeldorp Christel C Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Service, Brisbane, Australia.
Reif A Reif Andreas A Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
Rohde LA Rohde Luis Augusto LA ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Roussos P Roussos Panos P Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, New York, USA.
Schachar R Schachar Russell R Psychiatry, Neurosciences and Mental Health, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Sklar P Sklar Pamela P Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sonuga-Barke EJS Sonuga-Barke Edmund J S EJS Institute of Psychiatry, Psychology & Neuroscience, Kings College, London, UK.
Sullivan PF Sullivan Patrick F PF Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Thapar A Thapar Anita A MRC Centre for Neuropsychiatric Genetics & Genomics, School of Medicine, Cardiff University, Cardiff, UK.
Tung JY Tung Joyce Y JY 23andMe, Inc, Mountain View, CA, USA.
Waldman ID Waldman Irwin D ID Department of Psychology, Emory University, Atlanta, GA, USA.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Stefansson K Stefansson Kari K Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Nordentoft M Nordentoft Merete M Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
Hougaard DM Hougaard David M DM Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Werge T Werge Thomas T Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Mors O Mors Ole O Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
Mortensen PB Mortensen Preben Bo PB Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
Daly MJ Daly Mark J MJ Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
Faraone SV Faraone Stephen V SV Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA. sfaraone@childpsychresearch.org.
Børglum AD Børglum Anders D AD Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. anders@biomed.au.dk.
Neale BM Neale Benjamin M BM Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. bneale@broadinstitute.org.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Albayrak Özgür Ö
Anney Richard J L RJL
Arranz Maria Jesús MJ
Banaschewski Tobias J TJ
Bau Claiton C
Biederman Joseph J
Buitelaar Jan K JK
Casas Miguel M
Charach Alice A
Crosbie Jennifer J
Dempfle Astrid A
Doyle Alysa E AE
Ebstein Richard P RP
Elia Josephine J
Freitag Christine C
Föcker Manuel M
Gill Michael M
Grevet Eugenio E
Hawi Ziarih Z
Hebebrand Johannes J
Herpertz-Dahlmann Beate B
Hervas Amaia A
Hinney Anke A
Hohmann Sarah S
Holmans Peter P
Hutz Mara M
Ickowitz Abel A
Johansson Stefan S
Kent Lindsey L
Kittel-Schneider Sarah S
Lambregts-Rommelse Nanda N
Lehmkuhl Gerd G
Loo Sandra K SK
McGough James J JJ
Meyer Jobst J
Mick Eric E
Middletion Frank F
Miranda Ana A
Mota Nina Roth NR
Mulas Fernando F
Mulligan Aisling A
Nelson Freimer F
Nguyen T Trang TT
Oades Robert D RD
O'Donovan Michael C MC
Owen Michael J MJ
Palmason Haukur H
Ramos-Quiroga Josep Antoni JA
Renner Tobias J TJ
Ribasés Marta M
Rietschel Marcella M
Rivero Olga O
Romanos Jasmin J
Romanos Marcel M
Rothenberger Aribert A
Royers Herbert H
Sánchez-Mora Christina C
Scherag André A
Schimmelmann Benno G BG
Schäfer Helmut H
Sergeant Joseph J
Sinzig Judith J
Smalley Susan L SL
Steinhausen Hans-Christoph HC
Thompson Margaret M
Todorov Alexandre A
Vasquez Alejandro Arias AA
Walitza Susanne S
Wang Yufeng Y
Warnke Andreas A
Williams Nigel N
Witt Stephanie H SH
Yang Li L
Zayats Tetyana T
Zhang-James Yanli Y
Smith George Davey GD
Davies Gareth E GE
Ehli Erik A EA
Evans David M DM
Fedko Iryna O IO
Greven Corina U CU
Groen-Blokhuis Maria M MM
Guxens Monica M
Hammerschlag Anke R AR
Hartman Catharina A CA
Heinrich Joachim J
Jan Hottenga Jouke J
Hudziak James J
Jugessur Astanand A
Kemp John P JP
Krapohl Eva E
Murcia Mario M
Myhre Ronny R
Nolte Ilja M IM
Nyholt Dale R DR
Ormel Johan J
Ouwens Klaasjan G KG
Pappa Irene I
Pennell Craig E CE
Plomin Robert R
Ring Susan S
Standl Marie M
Stergiakouli Evie E
Pourcain Beate St BS
Stoltenberg Camilla C
Sunyer Jordi J
Thiering Elisabeth E
Tiemeier Henning H
Tiesler Carla M T CMT
Timpson Nicholas J NJ
Trzaskowski Maciej M
van der Most Peter Johannes PJ
Vilor-Tejedor Natalia N
Wang Carol A CA
Whitehouse Andrew J O AJO
Zhao Huiying H
Agee Michelle M
Alipanahi Babak B
Auton Adam A
Bell Robert K RK
Bryc Katarzyna K
Elson Sarah L SL
Fontanillas Pierre P
Furlotte Nicholas A NA
Hinds David A DA
Hromatka Bethann S BS
Huber Karen E KE
Kleinman Aaron A
Litterman Nadia K NK
McIntyre Matthew H MH
Mountain Joanna L JL
Northover Carrie A M CAM
Pitts Steven J SJ
Sathirapongsasuti J Fah JF
Sazonova Olga V OV
Shelton Janie F JF
Shringarpure Suyash S
Tian Chao C
Vacic Vladimir V
Wilson Catherine H CH
JOURNAL
VOLUME: 51
ISSUE: 1
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2019
MONTH: 01
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
CommentIn Nat Rev Neurol. 2019 Jan;15(1):4 30531819
CommentIn Nat Rev Genet. 2019 Feb;20(2):69 30532079
GRANTS
GRANTID AGENCY COUNTRY
G0300189 Medical Research Council United Kingdom
R01 MH094469 NIMH NIH HHS United States
R00 MH113823 NIMH NIH HHS United States
K01 DK114379 NIDDK NIH HHS United States
MC_UU_00011/1 Medical Research Council United Kingdom
S10 OD018522 NIH HHS United States
R01 MH101519 NIMH NIH HHS United States
R01 MH107649 NIMH NIH HHS United States
G19/2 Medical Research Council United Kingdom
U01 MH109536 NIMH NIH HHS United States
Wellcome Trust United Kingdom
U01 MH109539 NIMH NIH HHS United States
U01 MH094432 NIMH NIH HHS United States
MR/L010305/1 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Attention Deficit Disorder with Hyperactivity genetics
Brain physiology
Child physiology
Child, Preschool physiology
Cohort Studies physiology
Female physiology
Gene Expression Regulation genetics
Genetic Loci genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study methods
Humans methods
Male methods
Polymorphism, Single Nucleotide genetics
Risk genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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