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| PMID |
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| TITLE |
|
| Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. |
|
| ABSTRACT |
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| Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P = 0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P = 0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P = 0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD's etiology. |
| Copyright © 2013 Wiley Periodicals, Inc. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2013/03/17 |
| accepted |
2013/04/19 |
| entrez |
2013/06/04 06:00 |
| pubmed |
2013/06/04 06:00 |
| medline |
2013/10/18 06:00 |
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| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Yang L |
|
Yang |
Li |
L |
|
Key Laboratory of Mental Health, Ministry of Health, China. |
| Neale BM |
|
Neale |
Benjamin M |
BM |
|
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts. |
| Liu L |
|
Liu |
Lu |
L |
|
Key Laboratory of Mental Health, Ministry of Health, China. |
| Lee SH |
|
Lee |
S Hong |
SH |
|
The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia. |
| Wray NR |
|
Wray |
Naomi R |
NR |
|
The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia. |
| Ji N |
|
Ji |
Ning |
N |
|
Key Laboratory of Mental Health, Ministry of Health, China. |
| Li H |
|
Li |
Haimei |
H |
|
Key Laboratory of Mental Health, Ministry of Health, China. |
| Qian Q |
|
Qian |
Qiujin |
Q |
|
Key Laboratory of Mental Health, Ministry of Health, China. |
| Wang D |
|
Wang |
Dongliang |
D |
|
Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York. |
| Li J |
|
Li |
Jun |
J |
|
State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China. |
| Faraone SV |
|
Faraone |
Stephen V |
SV |
|
Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York. |
| Wang Y |
|
Wang |
Yufeng |
Y |
|
Key Laboratory of Mental Health, Ministry of Health, China. |
|
Psychiatric GWAS Consortium: ADHD Subgroup |
|
|
|
|
|
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Doyle |
Alysa E |
AE |
|
| Reif |
Andreas |
A |
|
| Rothenberger |
Aribert |
A |
|
| Franke |
Barbara |
B |
|
| Sonuga-Barke |
Edmund J S |
EJ |
|
| Steinhausen |
Hans-Christoph |
HC |
|
| Buitelaar |
Jan K |
JK |
|
| Kuntsi |
Jonna |
J |
|
| Biederman |
Joseph |
J |
|
| Lesch |
Klaus-Peter |
KP |
|
| Kent |
Lindsey |
L |
|
| Asherson |
Philip |
P |
|
| Oades |
Robert D |
RD |
|
| Loo |
Sandra K |
SK |
|
| Nelson |
Stan F |
SF |
|
| Faraone |
Stephen V |
SV |
|
| Smalley |
Susan L |
SL |
|
| Banaschewski |
Tobias |
T |
|
| Arias Vasquez |
Alejandro |
A |
|
| Todorov |
Alexandre |
A |
|
| Charach |
Alice |
A |
|
| Miranda |
Ana |
A |
|
| Warnke |
Andreas |
A |
|
| Thapar |
Anita |
A |
|
| Neale |
Benjamin M |
BM |
|
| Cormand |
Bru |
B |
|
| Freitag |
Christine |
C |
|
| Mick |
Eric |
E |
|
| Mulas |
Fernando |
F |
|
| Middleton |
Frank |
F |
|
| HakonarsonHakonarson |
Hakon |
H |
|
| Palmason |
Haukur |
H |
|
| Schäfer |
Helmut |
H |
|
| Roeyers |
Herbert |
H |
|
| McGough |
James J |
JJ |
|
| Romanos |
Jasmin |
J |
|
| Crosbie |
Jennifer |
J |
|
| Meyer |
Jobst |
J |
|
| Ramos-Quiroga |
Josep Antoni |
JA |
|
| Sergeant |
Joseph |
J |
|
| Elia |
Josephine |
J |
|
| Langely |
Kate |
K |
|
| Nisenbaum |
Laura |
L |
|
| Romanos |
Marcel |
M |
|
| Daly |
Mark J |
MJ |
|
| Ribasés |
Marta |
M |
|
| Gill |
Michael |
M |
|
| O'Donovan |
Michael |
M |
|
| Owen |
Michael |
M |
|
| Casas |
Miguel |
M |
|
| Bayés |
Mònica |
M |
|
| Lambregts-Rommelse |
Nanda |
N |
|
| Williams |
Nigel |
N |
|
| Holmans |
Peter |
P |
|
| Anney |
Richard J L |
RJ |
|
| Ebstein |
Richard P |
RP |
|
| Schachar |
Russell |
R |
|
| Medland |
Sarah E |
SE |
|
| Ripke |
Stephan |
S |
|
| Walitza |
Susanne |
S |
|
| Nguyen |
Thuy Trang |
TT |
|
| Renner |
Tobias J |
TJ |
|
| Hu |
Xiaolan |
X |
|
|
| JOURNAL |
|
| VOLUME: 162B |
| ISSUE: 5 |
| TITLE: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics |
| ISOABBREVIATION: Am J Med Genet B Neuropsychiatr Genet |
| YEAR: 2013 |
| MONTH: Jul |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1552-485X |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Am J Med Genet B Neuropsychiatr Genet |
| COUNTRY: United States |
| ISSNLINKING: 1552-4841 |
| NLMUNIQUEID: 101235742 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| MOP 74699 |
Canadian Institutes of Health Research |
Canada |
| U01 MH085518 |
NIMH NIH HHS |
United States |
| R01MH081803 |
NIMH NIH HHS |
United States |
| R01 MH062873 |
NIMH NIH HHS |
United States |
| U01 MH085515 |
NIMH NIH HHS |
United States |
| R01MH58277 |
NIMH NIH HHS |
United States |
| R01 MH058277 |
NIMH NIH HHS |
United States |
| R13 MH059126 |
NIMH NIH HHS |
United States |
| K23 MH066275 |
NIMH NIH HHS |
United States |
| R13MH059126 |
NIMH NIH HHS |
United States |
| R01 MH081803 |
NIMH NIH HHS |
United States |
| R01MH62873 |
NIMH NIH HHS |
United States |
| MOP 44070 |
Canadian Institutes of Health Research |
Canada |
| MOP 64277 |
Canadian Institutes of Health Research |
Canada |
|
Wellcome Trust |
United Kingdom |
| P30 HD004612 |
NICHD NIH HHS |
United States |
| U01MH085515 |
NIMH NIH HHS |
United States |
| K23MH066275-01 |
NIMH NIH HHS |
United States |
| U01MH085518 |
NIMH NIH HHS |
United States |
| G9810900 |
Medical Research Council |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Attention Deficit Disorder with Hyperactivity |
genetics |
| Case-Control Studies |
genetics |
| Child |
genetics |
| Female |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genome-Wide Association Study |
genetics |
| Humans |
genetics |
| Male |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
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|
