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
33495439
TITLE
Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder.
ABSTRACT
Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10 , OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h  = 0.34) when compared to ADHD without DBDs (h  = 0.20), high genetic correlations between ADHD + DBDs and aggressive (r  = 0.81) and anti-social behaviors (r  = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.
DATE PUBLISHED
2021 01 25
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2019/11/03
accepted 2020/11/30
entrez 2021/01/26 05:41
pubmed 2021/01/27 06:00
medline 2021/02/09 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Demontis D Demontis Ditte D Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. ditte@biomed.au.dk.
Walters RK Walters Raymond K RK Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Rajagopal VM Rajagopal Veera M VM Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
Waldman ID Waldman Irwin D ID Department of Psychology, Emory University, Atlanta, GA, USA.
Grove J Grove Jakob J Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
Als TD Als Thomas D TD Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
Dalsgaard S Dalsgaard Søren S National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
Ribasas M Ribasas Marta M Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
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 Maria M 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.
Nordentoft M Nordentoft Merete M Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mors O Mors Ole O Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark.
Mortensen PB Mortensen Preben Bo PB Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark.
ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
Cormand B Cormand Bru B Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Barcelona, Catalonia, Spain.
Hougaard DM Hougaard David M DM Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Neale BM Neale Benjamin M BM Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Franke B Franke Barbara B Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Faraone SV Faraone Stephen V SV Departments of Psychiatry and of 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.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Andreassen Ole A OA
Arranz Maria Jesús MJ
Banaschewski Tobias T
Bau Claiton C
Bellgrove Mark M
Biederman Joseph J
Brikell Isabell I
Buitelaar Jan K JK
Burton Christie L CL
Casas Miguel M
Crosbie Jennifer J
Doyle Alysa E AE
Ebstein Richard P RP
Elia Josephine J
Elizabeth Corfield C CC
Grevet Eugenio E
Grizenko Natalie N
Havdahl Alexandra A
Hawi Ziarih Z
Hebebrand Johannes J
Hervas Amaia A
Hohmann Sarah S
Haavik Jan J
Joober Ridha R
Kent Lindsey L
Kuntsi Jonna J
Langley Kate K
Larsson Henrik H
Lesch Klaus-Peter KP
Leung Patrick W L PWL
Liao Calwing C
Loo Sandra K SK
Martin Joanna J
Martin Nicholas G NG
Medland Sarah E SE
Miranda Ana A
Mota Nina Roth NR
Oades Robert D RD
Ramos-Quiroga Josep Antoni JA
Reif Andreas A
Rietschel Marcella M
Roeyers Herbert H
Rohde Luis Augusto LA
Rothenberger Aribert A
Rovira Paula P
Sánchez-Mora Cristina C
Schachar Russell James RJ
Sengupta Sarojini S
Artigas Maria Soler MS
Steinhausen Hans-Christoph HC
Thapar Anita A
Witt Stephanie H SH
Yang Li L
Zayats Tetyana T
Zhang-James Yanli Y
JOURNAL
VOLUME: 12
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2021
MONTH: 01
DAY: 25
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
U01 MH109514 NIMH NIH HHS United States
U01 MH109539 NIMH NIH HHS United States
R01 ES026993 NIEHS NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Attention Deficit Disorder with Hyperactivity genetics
Attention Deficit and Disruptive Behavior Disorders genetics
Child genetics
China epidemiology
Cohort Studies epidemiology
Comorbidity epidemiology
Europe epidemiology
Female epidemiology
Genetic Predisposition to Disease genetics
Genome-Wide Association Study methods
Humans methods
Male methods
Multifactorial Inheritance genetics
Polymorphism, Single Nucleotide genetics
Risk Factors genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's