Linkage study of catechol-O-methyltransferase and attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder is the most common child psychiatric disorder with a prevalence rate in an Ontario study of 9% in boys and 3% in girls [Szatmari et al., 1989]. This disorder is characterized by problems in the areas of attention, overactivity, impulse control, and distractibility. Strong evidence for a genetic component has been provided from twin, family, and adoption studies [for review see Levy et al., 1998] and molecular genetic studies are in progress by several groups worldwide. The Catechol-O-Methyltransferase (COMT) gene is an interesting candidate for ADHD as it is involved in the breakdown of dopamine and norepinephrine, neurotransmitters strongly implicated in the etiology of ADHD. In addition, children with velo-cardio-facial syndrome, a deletion syndrome of the chromosomal region 22q11 where the COMT gene has been localized, often have symptoms of ADHD suggesting this gene may have an etiological role in ADHD. In this study, we have tested for linkage in ADHD families using the functional polymorphism at codon 158 that determines COMT activity [Lachman et al., 1996] and analyzed the data with the transmission disequilibrium test (TDT). A total of 77 nuclear families collected from Toronto were genotyped. We find no evidence for linkage of this polymorphism and ADHD in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:710-713, 1999.