Showing papers by "Sarah Curran published in 2003"

The dopamine transporter gene is associated with attention deficit hyperactivity disorder in a Taiwanese sample.

Abstract: Genetic variation of the dopamine transporter gene (DAT1) is of particular interest in the study of attention-deficit hyperactivity disorder (ADHD), since stimulant drugs interact directly with the transporter protein. Association between ADHD and the 10-repeat allele of a 40-bp VNTR polymorphism that lies within the 3'-UTR of DAT1 was first reported in 1995, a finding that has been replicated in at least six independent samples from Caucasian populations. We analysed the DAT1 polymorphism in a sample of 110 Taiwanese probands with a DSM-IV diagnosis of ADHD and found evidence of increased transmission of the 10-repeat allele using TRANSMIT (chi(2)=10.8, 1 d.f., p=0.001, OR=2.9, 95% CI 1.4-6.3). These data give rise to a similar odds ratio to that observed in Caucasian poplulations despite a far higher frequency of the risk allele in this Taiwanese population; 82.3% in the un-transmitted parental alleles and 94.5% in the ADHD probands. These data support the role of DAT1 in ADHD susceptibility among Asian populations.

Polymorphisms in the dopamine D4 receptor gene and attention-deficit hyperactivity disorder.

Abstract: There is considerable evidence to support a role of dopamine-related genes in the molecular aetiology of attention-deficit hyperactivity disorder (ADHD). A 48 bp repeat in exon three of the dopamine D4 receptor gene has been widely studied in clinical ADHD samples, and a meta-analysis of published studies suggests it is associated with ADHD. A number of other polymorphisms across this gene have been characterised but not so thoroughly investigated in relation to ADHD. In this study we have genotyped five polymorphisms (a 120 bp promoter-region duplication, the -616 C/G substitution, the -521 C/T substitution, a poly-G repeat in intron 1, and the 48 bp exon 3 repeat) across the gene in a large clinical sample (n = 188) and their families. We found that none of the markers is individually associated with ADHD, although there is evidence to suggest that a haplotype of markers in the 5' promoter region of the gene (allele 2 of the 120 bp duplication, the C allele of the -616 substitution, and the C allele of the -521 substitution) may confer susceptibility.

CHIP: Defining a dimension of the vulnerability to attention deficit hyperactivity disorder (ADHD) using sibling and individual data of children in a community-based sample.

Abstract: We are taking a quantitative trait approach to the molecular genetic study of attention deficit hyperactivity disorder (ADHD) using a truncated case-control association design. An epidemiological sample of children aged 5 to 15 years was evaluated for symptoms of ADHD using a parent rating scale. Individuals scoring high or low on this scale were selected for further investigation with additional questionnaires and DNA analysis. Data in studies like this are typically complicated. In the study reported on here, individuals have from 1 to 4 questionnaires completed on them and the sample is composed of a mixture of singletons and siblings. In this paper, we describe how we used a genetic hierarchical model to fit our data, together with a twin dataset, in order to estimate genetic factor loadings. Correlation matrices were estimated for our data using a maximum likelihood approach to account for missing data. We describe how we used these results to create a composite score, the heritability of which was estimated to be acceptably high using the twin dataset. This score measures a quantitative dimension onto which molecular genetic data will be mapped.