Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11.

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Publication year
2008Source
American Journal of Human Genetics, 83, 1, (2008), pp. 99-105ISSN
Publication type
Article / Letter to editor

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Organization
Psychiatry
Health Evidence
Human Genetics
PI Group Memory and Emotion
Former Organization
F.C. Donders Centre for Cognitive Neuroimaging
Epidemiology, Biostatistics & HTA
Journal title
American Journal of Human Genetics
Volume
vol. 83
Issue
iss. 1
Page start
p. 99
Page end
p. 105
Subject
110 012 Social cognition of verbal communication; 150 000 MR Techniques in Brain Function; DCN 1: Perception and Action; DCN 2: Functional Neurogenomics; DCN 3: Neuroinformatics; IGMD 3: Genomic disorders and inherited multi-system disorders; NCEBP 9: Mental health; NCMLS 6: Genetics and epigenetic pathways of disease; UMCN 3.2: Cognitive neurosciences; UMCN 5.1: Genetic defects of metabolismAbstract
ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores > or = 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders.
This item appears in the following Collection(s)
- Academic publications [202923]
- Donders Centre for Cognitive Neuroimaging [3357]
- Electronic publications [101091]
- Faculty of Medical Sciences [80072]
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