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PMID: 18973233 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Multivariate genomewide linkage scan of neurocognitive traits and ADHD symptoms: suggestive linkage to 3q13.

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics ·Vol. 147B ·No. 8 ·2008-12-05 ·Pages 1399-411

Doyle AE, Ferreira MA, Sklar PB, Lasky-Su J, Petty C, Fusillo SJ, Seidman LJ, Willcutt EG, Smoller JW, Purcell S, Biederman J, Faraone SV

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.

MeSH Terms
Adolescent Attention Deficit Disorder with Hyperactivity/diagnosis,genetics Child Chromosome Mapping Chromosomes, Human, Pair 3/genetics Genetic Linkage Genome, Human Genotype Humans Interviews as Topic Neuropsychological Tests Parents Quantitative Trait Loci/genetics Siblings
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Doyle Alysa E
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. [email protected]
Ferreira Manuel A R
Sklar Pamela B
Lasky-Su Jessica
Petty Carter
Fusillo Steven J
Seidman Larry J
Willcutt Erik G
Smoller Jordan W
Purcell Shaun
Biederman Joseph
Faraone Stephen V
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Article Info
Journal
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Abbr.
Am J Med Genet B Neuropsychiatr Genet
ISSN
1552-485X
DOI
10.1002/ajmg.b.30868
Email
[email protected]
Published
2008-12-05
Pages
1399-411
Language
English
Region
United States
NLM ID
101235742
PMCID
PMC4002289
Subset
IM
Grants
NICHD NIH HHS · R01HD37694 · United States
NIMH NIH HHS · R21MH080730 · United States
NICHD NIH HHS · R01 HD037694 · United States
NIMH NIH HHS · R21 MH080730 · United States
NIMH NIH HHS · R21 MH080730-02 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1002/ajmg.b.30868 PMC Full Text View journal details
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