1. ¹Genetics Program, Michigan State University, East Lansing, MI, USA
2. ²Department of Psychology, Michigan State University, East Lansing, MI, USA
3. ³Department of Psychology, Emory University, Atlanta, GA, USA
4. ⁴Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA
5. ⁵Peds/Hum. Dev., Michigan State University, East Lansing, MI 48824, USA

Correspondence: Professor KH Friderici, Department of Microbiology & Molecular Genetics, Michigan State University, 5163 Biomedical Physical Sciences Bldg, East Lansing, MI 48824, USA. E-mail: frideric@msu.edu

Received 7 June 2004; Revised 1 September 2004; Accepted 15 September 2004; Published online 2 November 2004.

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a heritable disorder, prevalent from childhood through adulthood. Although the noradrenergic (NA) system is thought to mediate a portion of the pathophysiology of ADHD, genes in this pathway have not been investigated as frequently as those in the dopaminergic system. Previous association studies of one candidate gene in the NA system, ADRA2A, showed inconsistent results with regard to an MspI polymorphism. In the current study, two nearby single-nucleotide polymorphisms, which define HhaI and DraI restriction fragment length polymorphisms, were also genotyped and were in significant linkage disequilibrium with the MspI RFLP. Transmission disequilibrium tests (TDTs) in a sample of 177 nuclear families showed significant association and linkage of the DraI polymorphism with the ADHD combined subtype (P=0.03), and the quantitative TDT showed association of this polymorphism with the inattentive (P=0.003) and hyperactive-impulsive (P=0.015) symptom dimensions. The haplotype that contained the less common allele of the DraI polymorphism likewise showed a strong relationship with the inattentive (P=0.001) and hyperactive-impulsive (P=0.004) symptom dimensions. This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism.