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, K., Asherson, P., Sham, P.C., Anney, R.J.L., Franke, B., Buitelaar, J.K., Ebstein, R., Gill, M., Brookes, K.J., Buschgens, C., Cambell, D., Chen, W., Christiansen, H., Fliers, E., Gabriëls, I., Johansson, L., Marco, R., Mulas, F., Müller, U.C., Mulligan, A., Neale, B.M., Rijsdijk, F., Rommelse, N., Uebel, H., Psychogiou, L., Xu, X., Banaschewski, T., Sonuga-Barke, E.J.S., Eisenberg, J., Manor, I., Miranda, A., Oades, R.D., Roeyers, H., Rothenberger, A., Sergeant, J.A., Steinhausen, H.-C., Taylor, E.A., Thompson, M., Faraone, S.V., 2011. Linkage to Chromosome 1p36 for Attention Deficit Hyperactivity Disorder Traits in School and Home Settings. https://doi.org/10.1016/j.biopsych.2008.02.024
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