Failure to replicate an association between the catechol-O-methyltransferase polymorphism and attention deficit hyperactivity disorder in a second, independently recruited Israeli cohort

Attention deficit hyperactivity disorder (ADHD) is a developmental syndrome expressed along three domains: inattention, hyperactive-impulsive, and combined type. Both environmental and genetic factors contribute to the etiology of this complex disease. We previously reported an association in 48 ADHD triads (both parents and proband) between the catechol-O-methyl- transferase (COMT) polymorphism (especially the high enzyme activity val allele) and the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) combined category (excluding inattention) of ADHD (however, see erratum, Am. J. Med. Genet. [Neuropsychiatr. Genet.] 96:893). In the current report, we attempted to replicate this finding in an independently recruited group of 70 nuclear families using the haplotype relative risk design. In the current investigation, no evidence for association of the COMT polymorphism and ADHD (or any of the DSM IV subtypes) was observed in either the current cohort or the expanded cohort of 118 Israeli triads. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:858-860, 2000.