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
23599091
TITLE
High loading of polygenic risk for ADHD in children with comorbid aggression.
ABSTRACT
OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.
DATE PUBLISHED
2013 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2013/04/20 06:00
pubmed 2013/04/20 06:00
medline 2013/10/01 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hamshere ML Hamshere Marian L ML MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK.
Langley K Langley Kate K
Martin J Martin Joanna J
Agha SS Agha Sharifah Shameem SS
Stergiakouli E Stergiakouli Evangelia E
Anney RJ Anney Richard J L RJ
Buitelaar J Buitelaar Jan J
Faraone SV Faraone Stephen V SV
Lesch KP Lesch Klaus-Peter KP
Neale BM Neale Benjamin M BM
Franke B Franke Barbara B
Sonuga-Barke E Sonuga-Barke Edmund E
Asherson P Asherson Philip P
Merwood A Merwood Andrew A
Kuntsi J Kuntsi Jonna J
Medland SE Medland Sarah E SE
Ripke S Ripke Stephan S
Steinhausen HC Steinhausen Hans-Christoph HC
Freitag C Freitag Christine C
Reif A Reif Andreas A
Renner TJ Renner Tobias J TJ
Romanos M Romanos Marcel M
Romanos J Romanos Jasmin J
Warnke A Warnke Andreas A
Meyer J Meyer Jobst J
Palmason H Palmason Haukur H
Vasquez AA Vasquez Alejandro Arias AA
Lambregts-Rommelse N Lambregts-Rommelse Nanda N
Roeyers H Roeyers Herbert H
Biederman J Biederman Joseph J
Doyle AE Doyle Alysa E AE
Hakonarson H Hakonarson Hakon H
Rothenberger A Rothenberger Aribert A
Banaschewski T Banaschewski Tobias T
Oades RD Oades Robert D RD
McGough JJ McGough James J JJ
Kent L Kent Lindsey L
Williams N Williams Nigel N
Owen MJ Owen Michael J MJ
Holmans P Holmans Peter P
O'Donovan MC O'Donovan Michael C MC
Thapar A Thapar Anita A
INVESTIGATORS
JOURNAL
VOLUME: 170
ISSUE: 8
TITLE: The American journal of psychiatry
ISOABBREVIATION: Am J Psychiatry
YEAR: 2013
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1535-7228
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Psychiatry
COUNTRY: United States
ISSNLINKING: 0002-953X
NLMUNIQUEID: 0370512
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
G9810900 Medical Research Council United Kingdom
U01 HG006830 NHGRI NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aggression psychology
Anxiety Disorders psychology
Attention Deficit Disorder with Hyperactivity psychology
Child psychology
Child, Preschool psychology
Comorbidity psychology
Conduct Disorder psychology
Depressive Disorder psychology
Female psychology
Genetic Predisposition to Disease genetics
Genetic Variation genetics
Humans genetics
Male genetics
Multifactorial Inheritance genetics
United Kingdom genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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