Zhou, K., Asherson, P., Sham, P., Anney, R. J. L., Franke, B., Buitelaar, J., Ebstein, R. P., Gill, M., Brookes, K-J., Buschgens, C., Campbell, D., Chen, W., Christiansen, C., Fliers, E., Gabriëls, I., Johansson, L., Marco, R., Mulas, F., Müller, U. C., Mulligan, A., Neale, B. M., Rijsdijk, F., Rommelse, N. N. J., 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. (2008)
Linkage to Chromosome 1p36 for Attention Deficit Hyperactivity Disorder Traits in School and Home Settings. Biological Pychiatry, 64, 571-576. doi:10.1016/j.biopsych.2008.02.024 (request a copy). View Article

Background: Limited success has been achieved through previous 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.

Methods: A set of 1,094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative 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<0.04. Setting-specific suggestive linkage signals were also found: 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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