QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms

Current developments in molecular genetics have led to a rapid increase in research aimed at the identification of genetic variation that influences c omplex human phenotypes. One phenotype that has aroused a great deal of int erest is the behavioral trait hyperactivity and the related clinical disord er attention-deficit hyperactivity disorder (ADHD). The driving force behin d the molecular genetic research in this area is the overwhelming evidence from quantitative genetic studies that show high heritablility (h(2) = 0.7- 0.9) for the behaviors characterizing the diagnosis of ADHD, whether the di sorder is viewed as a categorical entity or a continuous trait. To date, mo lecular studies have aimed at identifying susceptibility genes for ADHD, de fined using operational diagnostic criteria, and have focused on variation within genes that regulate dopamine neurotransmission. Several studies repo rt ADHD to be associated with the 7-repeat allele of a 48 bp repeat polymor phism (DRD4-7) in exon 3 of the dopamine D4 receptor gene (DRD4). In this s tudy, we take a dimensional perspective of ADHD and examine the relationshi p of this DRD4 polymorphism in a sample of children selected from the gener al population on the basis of high and low scores on the five ADHD items of the Strengths and Difficulties Questionnaire (SDQ) as rated by their paren ts. We found a significant relationship between DRD4-7 and high-scoring ind ividuals [chi-square = 8.63; P = 0.003; OR = 2.09 (95% CI 1.24 < OR < 3.54) , F-statistic = 7.245; P = 0.0081, (C) 2001 Wiley-Liss, Inc.