Genetic Epidemiology, Psychiatric Genetics, Asthma 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
23527680
TITLE
Genome-wide association study of inattention and hyperactivity-impulsivity measured as quantitative traits.
ABSTRACT
Genome-wide association studies (GWAS) of attention-deficit/hyperactivity disorder (ADHD) offer the benefit of a hypothesis-free approach to measuring the quantitative effect of genetic variants on affection status. Generally the findings of GWAS relying on ADHD status have been non-significant, but the one study using quantitative measures of symptoms found SLC9A9 and SLC6A1 were associated with inattention and hyperactivity-impulsivity. Accordingly, we performed a GWAS using quantitative measures of each ADHD subtype measured with the Strengths and Weaknesses of ADHD and Normal Behaviour (SWAN) scale in two community-based samples. This scale captures the full range of attention and kinetic behavior; from high levels of attention and appropriate activity to the inattention and hyperactivity-impulsivity associated with ADHD within two community-based samples. Our discovery sample comprised 1,851 participants (mean age = 22.8 years [4.8]; 50.6% female), while our replication sample comprised 155 participants (mean age = 26.3 years [3.1]; 68.4% females). Age, sex, age ? sex, and age2 were included as covariates and the results from each sample were combined using meta-analysis, then analyzed with a gene-based test to estimate the combined effect of markers within genes. We compare our results with markers that have previously been found to have a strong association with ADHD symptoms. Neither the GWAS nor subsequent meta-analyses yielded genome-wide significant results; the strongest effect was observed at rs2110267 (4.62 ? 10-7) for symptoms of hyperactivity-impulsivity. The strongest effect in the gene-based test was for GPR139 on symptoms of inattention (6.40 ? 10-5). Replication of this study with larger samples will add to our understanding of the genetic etiology of ADHD.
DATE PUBLISHED
2013 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2013/03/27 06:00
pubmed 2013/03/27 06:00
medline 2013/06/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ebejer JL Ebejer Jane L JL School of Environmental and Rural Sciences, University of New England, Armidale, New South Wales, Australia. jebejer@une.edu.au
Duffy DL Duffy David L DL
van der Werf J van der Werf Julius J
Wright MJ Wright Margaret J MJ
Montgomery G Montgomery Grant G
Gillespie NA Gillespie Nathan A NA
Hickie IB Hickie Ian B IB
Martin NG Martin Nicholas G NG
Medland SE Medland Sarah E SE
INVESTIGATORS
JOURNAL
VOLUME: 16
ISSUE: 2
TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies
ISOABBREVIATION: Twin Res Hum Genet
YEAR: 2013
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 1832-4274
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Twin Res Hum Genet
COUNTRY: England
ISSNLINKING: 1832-4274
NLMUNIQUEID: 101244624
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
R00DA023549 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Attention Deficit Disorder with Hyperactivity psychology
Australia epidemiology
Cohort Studies epidemiology
Diseases in Twins genetics
Female genetics
Genetics, Behavioral genetics
Genome-Wide Association Study genetics
Humans genetics
Impulsive Behavior genetics
Male genetics
Phenotype genetics
Quantitative Trait, Heritable genetics
Registries genetics
Twins, Dizygotic genetics
Twins, Monozygotic genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's