Linkage to Chromosome 1p36 for Attention Deficit Hyperactivity Disorder Traits in School and Home Settings

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

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.

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Zhou, Kaixin / Asherson, Philip / Sham, Pak C. / et al: Linkage to Chromosome 1p36 for Attention Deficit Hyperactivity Disorder Traits in School and Home Settings. 2011.

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