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
18973233
TITLE
Multivariate genomewide linkage scan of neurocognitive traits and ADHD symptoms: suggestive linkage to 3q13.
ABSTRACT
Family and twin studies suggest that a range of neurocognitive traits index the inherited liability to ADHD; however, the utility of such measures as endophenotypes in molecular genetic studies remains largely untested. The current article examined whether the inclusion of neurocognitive measures in a genomewide linkage analysis of ADHD could aid in identifying QTL linked to the behavioral symptoms of the condition. Data were from an affected sibling pair linkage study of DSM-IV ADHD conducted at Massachusetts General Hospital. The sample included 1,212 individuals from 271 families. ADHD symptoms were assessed with the K-SADS-E. The neurocognitive battery included Wechsler Intelligence Scales subtests, the Stroop, the Wisconsin Card Sorting Test (WCST), the Rey-Osterreith Complex Figure, a working memory CPT, the CVLT and WRAT-III subscales. Evidence for linkage was assessed using a simulation-based method that combines information from univariate analyses into the equivalent of a multivariate test. After correction for multiple trait testing, a region on chromosome 3q13 showed suggestive linkage to all neurocognitive traits examined and inattention symptoms of ADHD. The second highest peak occurred on 22q12 but showed linkage to a single subscale of the WCST. In univariate analysis, this region retained criteria for suggestive linkage to this measure after correction for multiple trait testing. Our primary findings raise the possibility that one or more genes on 3q13 influence neurocognitive functions and behavioral symptoms of inattention. Overall, these data support the utility of neurocognitive traits as ADHD endophenotypes, but also highlight their limited genetic overlap with the disorder.
Copyright 2008 Wiley-Liss, Inc.
DATE PUBLISHED
2008 Dec 5
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2008/11/01 09:00
medline 2009/01/07 09:00
entrez 2008/11/01 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Doyle AE Doyle Alysa E AE Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. aedoyle@partners.org
Ferreira MA Ferreira Manuel A R MA
Sklar PB Sklar Pamela B PB
Lasky-Su J Lasky-Su Jessica J
Petty C Petty Carter C
Fusillo SJ Fusillo Steven J SJ
Seidman LJ Seidman Larry J LJ
Willcutt EG Willcutt Erik G EG
Smoller JW Smoller Jordan W JW
Purcell S Purcell Shaun S
Biederman J Biederman Joseph J
Faraone SV Faraone Stephen V SV
INVESTIGATORS
JOURNAL
VOLUME: 147B
ISSUE: 8
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: 2008
MONTH: Dec
DAY: 5
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
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
R01HD37694 NICHD NIH HHS United States
R21 MH080730-02 NIMH NIH HHS United States
R21MH080730 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Attention Deficit Disorder with Hyperactivity genetics
Child genetics
Chromosome Mapping genetics
Chromosomes, Human, Pair 3 genetics
Genetic Linkage genetics
Genome, Human genetics
Genotype genetics
Humans genetics
Interviews as Topic genetics
Neuropsychological Tests genetics
Parents genetics
Quantitative Trait Loci genetics
Siblings genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS76298 NLM
PMC4002289 NLM
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