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PMID |
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TITLE |
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Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder. |
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ABSTRACT |
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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 SNP = 0.34) when compared to ADHD without DBDs (h SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 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. |
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DATE PUBLISHED |
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HISTORY |
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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 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Demontis D |
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Demontis |
Ditte |
D |
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Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. ditte@biomed.au.dk. |
Walters RK |
|
Walters |
Raymond K |
RK |
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Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. |
Rajagopal VM |
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Rajagopal |
Veera M |
VM |
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Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. |
Waldman ID |
|
Waldman |
Irwin D |
ID |
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Department of Psychology, Emory University, Atlanta, GA, USA. |
Grove J |
|
Grove |
Jakob |
J |
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Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. |
Als TD |
|
Als |
Thomas D |
TD |
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Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. |
Dalsgaard S |
|
Dalsgaard |
Søren |
S |
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National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark. |
Ribasés M |
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Ribasés |
Marta |
M |
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Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain. |
Bybjerg-Grauholm J |
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Bybjerg-Grauholm |
Jonas |
J |
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Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. |
Bækvad-Hansen M |
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Bækvad-Hansen |
Maria |
M |
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Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. |
Werge T |
|
Werge |
Thomas |
T |
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Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. |
Nordentoft M |
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Nordentoft |
Merete |
M |
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. |
Mors O |
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Mors |
Ole |
O |
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Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark. |
Mortensen PB |
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Mortensen |
Preben Bo |
PB |
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Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark. |
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ADHD Working Group of the Psychiatric Genomics Consortium (PGC) |
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Cormand B |
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Cormand |
Bru |
B |
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Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Barcelona, Catalonia, Spain. |
Hougaard DM |
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Hougaard |
David M |
DM |
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Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. |
Neale BM |
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Neale |
Benjamin M |
BM |
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Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. |
Franke B |
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Franke |
Barbara |
B |
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Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. |
Faraone SV |
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Faraone |
Stephen V |
SV |
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Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA. sfaraone@childpsychresearch.org. |
Børglum AD |
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Børglum |
Anders D |
AD |
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Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. anders@biomed.au.dk. |
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INVESTIGATORS |
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LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
Andreassen |
Ole A |
OA |
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Arranz |
Maria Jesús |
MJ |
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Banaschewski |
Tobias |
T |
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Bau |
Claiton |
C |
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Bellgrove |
Mark |
M |
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Biederman |
Joseph |
J |
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Brikell |
Isabell |
I |
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Buitelaar |
Jan K |
JK |
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Burton |
Christie L |
CL |
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Casas |
Miguel |
M |
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Crosbie |
Jennifer |
J |
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Doyle |
Alysa E |
AE |
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Ebstein |
Richard P |
RP |
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Elia |
Josephine |
J |
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Elizabeth |
Corfield C |
CC |
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Grevet |
Eugenio |
E |
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Grizenko |
Natalie |
N |
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Havdahl |
Alexandra |
A |
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Hawi |
Ziarih |
Z |
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Hebebrand |
Johannes |
J |
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Hervas |
Amaia |
A |
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Hohmann |
Sarah |
S |
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Haavik |
Jan |
J |
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Joober |
Ridha |
R |
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Kent |
Lindsey |
L |
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Kuntsi |
Jonna |
J |
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Langley |
Kate |
K |
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Larsson |
Henrik |
H |
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Lesch |
Klaus-Peter |
KP |
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Leung |
Patrick W L |
PWL |
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Liao |
Calwing |
C |
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Loo |
Sandra K |
SK |
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Martin |
Joanna |
J |
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Martin |
Nicholas G |
NG |
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Medland |
Sarah E |
SE |
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Miranda |
Ana |
A |
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Mota |
Nina Roth |
NR |
|
Oades |
Robert D |
RD |
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Ramos-Quiroga |
Josep Antoni |
JA |
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Reif |
Andreas |
A |
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Rietschel |
Marcella |
M |
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Roeyers |
Herbert |
H |
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Rohde |
Luis Augusto |
LA |
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Rothenberger |
Aribert |
A |
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Rovira |
Paula |
P |
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Sánchez-Mora |
Cristina |
C |
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Schachar |
Russell James |
RJ |
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Sengupta |
Sarojini |
S |
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Artigas |
Maria Soler |
MS |
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Steinhausen |
Hans-Christoph |
HC |
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Thapar |
Anita |
A |
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Witt |
Stephanie H |
SH |
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Yang |
Li |
L |
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Zayats |
Tetyana |
T |
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Zhang-James |
Yanli |
Y |
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JOURNAL |
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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 |
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MEDLINE JOURNAL |
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MEDLINETA: Nat Commun |
COUNTRY: England |
ISSNLINKING: 2041-1723 |
NLMUNIQUEID: 101528555 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Meta-Analysis |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
ErratumIn |
Nat Commun. 2021 Feb 15;12(1):1166 |
33589642 |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
G0300189 |
Medical Research Council |
United Kingdom |
R01 ES026993 |
NIEHS NIH HHS |
United States |
U01 MH109514 |
NIMH NIH HHS |
United States |
U01 MH109539 |
NIMH NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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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 |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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