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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 |
|
| 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. |
| Ribasés M |
|
Ribasés |
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 |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| ErratumIn |
Nat Commun. 2021 Feb 15;12(1):1166 |
33589642 |
|
|
| GRANTS |
|
| 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 |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
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| 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 |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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