The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder : association signals in DRD4, DAT1 and 16 other genes

Brookes, K. and Xu, X. and Chen, W. and Zhou, Kaixin and Neale, Ben and Lowe, N. and Anney, R. and Franke, B. and Gill, M. and Ebstein, Richard and Buitelaar, Jan and Sham, P and Campbell, D. and Knight, Jo and Andreou, Penny and Altink, Marieke and Arnold, R. and Boer, F and Buschgens, C and Butler, L and Christiansen, H and Feldman, L and Fleischman, K and Fliers, E and Howe-Forbes, R and Goldfarb, A and Heise, A and Gabriëls, I and Korn-Lubetzki, I and Johansson, L and Marco, R and Medad, S and Minderaa, R and Mulas, F and Müller, U and Mulligan, A and Rabin, K and Rommelse, N and Sethna, V and Sorohan, J and Uebel, H and Psychogiou, L and Weeks, A and Barrett, R and Craig, I and Banaschewski, T and Sonuga-Barke, E and Eisenberg, J and Kuntsi, J and Manor, I and McGuffin, P and Miranda, A and Oades, R D and Plomin, R and Roeyers, H and Rothenberger, A and Sergeant, J and Steinhausen, H-C and Taylor, E and Thompson, M and Faraone, S V and Asherson, P (2006) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder : association signals in DRD4, DAT1 and 16 other genes. Molecular Psychiatry, 11 (10). pp. 934-953. ISSN 1359-4184

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.