1. ¹MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, UK
2. ²Department of Psychiatry, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland
3. ³Department of Psychiatry, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands
4. ⁴S Herzog Memorial Hospital, Jerusalem, Israel
5. ⁵Triversum, Alkmaar, Holland
6. ⁶Amsterdam Medical Centre de Bascule, Amsterdam, Holland
7. ⁷University Clinic for Child and Adolescent Psychiatry, Essen, Germany
8. ⁸ADHD Clinic, Geha Mental Health Center, Petak-Tikvah, Israel
9. ⁹Child and Adolescent Psychiatry, University of Göttingen, Göttingen, Germany
10. ¹⁰Departments of Experimental Clinical Health Psychology, Ghent University, Ghent, Belgium
11. ¹¹Shaare Zedek Medical Center, Jerusalem, Israel
12. ¹²Department of Developmental and Educational Psychology, University of Valencia, Valencia, Spain
13. ¹³University Centre for Child and Adolescence Psychiatry, University Medical Centre, Groningen, The Netherlands
14. ¹⁴Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland
15. ¹⁵Vrije Universiteit, De Boelelaan, Amsterdam, Holland
16. ¹⁶School of Psychology, University of Southampton, Highfield, Southampton, UK
17. ¹⁷Departments of Psychiatry and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA

Correspondence: Professor P Asherson, MRC Social Genetic Developmental Psychiatry, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. E-mail: p.asherson@iop.kcl.ac.uk

Received 6 March 2006; Accepted 5 June 2006; Published online 8 August 2006.

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 1038 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.