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

Full Abstract

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.

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Author information

Author/s: Rommelse, Nanda N J (NN); Arias-Vásquez, Alejandro (A); Altink, Marieke E (ME); Buschgens, Cathelijne J M (CJ); Fliers, Ellen (E); Asherson, Philip (P); Faraone, Stephen V (SV); Buitelaar, Jan K (JK); Sergeant, Joseph A (JA); Oosterlaan, Jaap (J); Franke, Barbara (B);

Affiliation: Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands.

Grants: R01 MH62873-01A1 (Agency:United States NIMH)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: American journal of human genetics (Am J Hum Genet), published in United States. (Language: eng)

Reference: 2008-Jul; vol 83 (issue 1) : pp 99-105

Dates: Created 2008/07/08; Completed 2008/07/29; Revised 2008/08/22;

PMID: 18599010, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

ErratumIn: Am J Hum Genet. 2008 Aug;83(2):294.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Attention Deficit Disorder with Hyperactivity - epidemiology; genetics
Case-Control Studies
Child
Chromosome Mapping
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 2
Cognition
Female
Genetic Predisposition to Disease
Genome
Humans

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