Abstract
Molecular studies of attention deficit hyperactivity disorder (ADHD) have identified susceptibility genes for the categorically diagnosed disorder using operational diagnostic criteria. Here, we take a QTL approach to mapping genes for ADHD using a composite continuous index of ADHD behavior in a large epidemiological sample. Previous studies of clinical ADHD suggest that two functional polymorphisms in the serotonin transporter gene (SLC6A4), one in the 5โฒโregulatory region of the gene (5โHTTLPR) and the other a VNTR (5โHTTVNTR) in the second intron, as well as a single nucleotide polymorphism in the 3โฒโuntranslated region (3โฒโUTR SNP), may be associated with the disorder. Here, we investigate these polymorphisms as well as an additional ten SNPs spread across the gene. We found significant association with the long (L) allele of the 5โHTTLPR; Pโ=โ0.019, but neither the 5โHTTVNTR nor the 3โฒโUTR SNP were significantly associated. Significant associations (Pโ<โ0.05) were found for a further 5 the 10 other markers tested. We found evidence for two haplotype blocks spanning the region. We found strong evidence for association with the first haplotype block (comprised of four markers), with the significance of a combined primary and secondary test of association reaching an empirical P valueโ=โ0.0054 for the global test and an empirical P valueโ=โ0.00081 for the largest local test. Thus, we show here that SLC6A4, which has a major influence on brain serotonin availability, may be a QTL for ADHD. ยฉ 2005 WileyโLiss, Inc.