Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings

Kaixin Zhou, Philip Asherson, Pak Sham, Barbara Franke, Richard J L Anney, Jan Buitelaar, Richard Ebstein, Michael Gill, Keeley Brookes, Cathelijne Buschgens, Desmond Campbell, Wai Chen, Hanna Christiansen, Ellen Fliers, Isabel Gabriëls, Lena Johansson, Rafaela Marco, Fernando Mulas, Ueli Müller, Aisling MulliganBenjamin M Neale, Fruhling Rijsdijk, Nanda Rommelse, Henrik Uebel, Lamprini Psychogiou, Xiaohui Xu, Tobias Banaschewski, Edmund Sonuga-Barke, Jacques Eisenberg, Iris Manor, Ana Miranda, Robert D Oades, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Hans-Christoph Steinhausen, Eric Taylor, Margaret Thompson, Stephen V Faraone

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL).

METHODS: A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collected and standardized according to a population sample of 8000 children to reflect the developmental nature and gender prevalence difference of ADHD. Univariate linkage test was performed on both traits and their mean score.

RESULTS: A significant common linkage locus was found at chromosome 1p36 with a locus-specific heritability of 5.1% and a genomewide empirical p < .04. Setting-specific suggestive linkage signals were also found: logarithm of odds (LOD) = 2.2 at 9p23 for home trait and LOD = 2.6 at 11q21 for school trait.

CONCLUSIONS: These results indicate that given large samples with proper phenotypic measures, searching for ADHD genes with a QTL strategy is an important alternative to using the clinical diagnosis. The fact that our linkage region 1p36 overlaps with the dyslexia QTL DYX8 further suggests it is potentially a pleiotropic locus for ADHD and dyslexia.

Original languageEnglish
Pages (from-to)571-6
Number of pages6
JournalBiological Psychiatry
Volume64
Issue number7
DOIs
Publication statusPublished - 1 Oct 2008

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