Linkage to chromosome 1p36 for Attention Deficit Hyperactivity Disorder traits in school and home settings

Zhou, K., Asherson, P., Sham, P., Franke, B., Anney, R.J., Buitelaar, J., Ebstein, R., Gill, M., Brookes, K., Buschgens, C., Campbell, D., Chen, W., Christiansen, H., Fliers, E., Gabriels, I., Johansson, L., Marco, R., Mulas, F., Mueller, U., Mulligan, A., Neale, B.M., Rijsdijk, F., Rommelse, N., Uebel, H., Psychogiou, L., Xu, X., Banaschewski, T., Sonuga-Barke, E., Eisenberg, J., Manor, I., Miranda, A., Oades, R.D., Roeyers, H., Rothenberger, A., Sergeant, J., Steinhausen, H.C., Taylor, E., Thompson, M. and Faraone, S.V. (2008) Linkage to chromosome 1p36 for Attention Deficit Hyperactivity Disorder traits in school and home settings. Biological Psychology. (doi:10.1016/j.biopsych.2008.02.024).

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.

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