1. ¹Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany
2. ²Institute of Medical Biometry and Epidemiology, University of Marburg, Marburg, Germany
3. ³Molecular Genetics and Gene Mapping Center, Max Delbrück Center Berlin-Buch, Berlin, Germany
4. ⁴Cologne Center for Genomics, University of Cologne, Cologne, Germany
5. ⁵Department of Child and Adolescent Psychiatry, RWTH Aachen, Aachen, Germany
6. ⁶Psychiatric Clinic for Children and Adolescents, Regensburg, Germany
7. ⁷Department of Child and Adolescent Psychiatry, University of Marburg, Marburg, Germany
8. ⁸Department of Child and Adolescent Psychiatry, University of Würzburg, Würzburg, Germany
9. ⁹Department of Child and Adolescent Psychiatry, University of Lübeck, Lübeck, Germany
10. ¹⁰Department of Psychiatry, University of Marburg, Marburg, Germany

Correspondence: Professor J Hebebrand, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Virchowstr. 174, D-45147 Essen, Germany. E-mail: Johannes.Hebebrand@uni-duisburg-essen.de

Received 17 May 2005; Revised 9 August 2005; Accepted 1 September 2005; Published online 11 October 2005.

Abstract

Three groups have previously performed genome scans in attention-deficit/hyperactivity disorder (ADHD); linkage to chromosome 5p13 was detected in all of the respective studies. In the current study, we performed a whole-genome scan with 102 German families with two or more offspring who currently fulfilled the diagnostic criteria for ADHD. Including subsequent fine mapping on chromosome 5p, a total of 523 markers were genotyped. The highest nonparametric multipoint LOD score of 2.59 (empirical genome-wide significance 0.1) was obtained for chromosome 5p at 17 cM (according to the Marshfield map). Subsequent analyses revealed (a) a higher LOD score of 3.37 at 39 cM for a quantitative severity score based on symptoms of inattention than for hyperactivity/impulsivity (LOD score of 1.11 at 59 cM), and (b) an HLOD of 4.75 (empirical genome-wide significance 0.001) based on a parametric model assuming dominant inheritance. The locus of the solute carrier 6A3 (SLC6A3; dopamine transporter 1; DAT1) localizes to 5p15.33; the gene has repeatedly been implicated in the etiology of ADHD. However, in our sample the DAT1 VNTR did not show association with ADHD. We additionally identified nominal evidence for linkage to chromosomes 6q, 7p, 9q, 11 q, 12q and 17p, which had also been identified in previous scans. Despite differences in ethnicity, ascertainment and phenotyping schemes, linkage results in ADHD appear remarkably consistent.