ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Xu X, 2009(b)19196467
Citation	Xu X., Mill J., Sun B., Chen C. K., Huang Y. S., Wu Y. Y. and Asherson P. (2009) "Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder." BMC Psychiatry, 9: 3.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	197 families from United Kingdom, 212 families from Taiwan
Predominant Ethnicity	Caucasian, Mongoloid
Population	United Kingdom, Taiwan
Age Group	Children/Adolescents : aged 5-15 years; mean age 10.41 years (SD=2.34) for United Kingdom sample and 8.96 years (SD=2.60) for Taiwan sample.

Detail Info

Summary	To investigate the association between the polymorphisms -67A/T (rs2975226) and -839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the United Kingdom (n=197) and Taiwan (n=212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT). A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (P-value=0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the United Kingdom and Taiwan (P-value=0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations. The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.
Total Sample	For the United Kingdom sample, patients were composed of 197 ADHD combined subtype probands, from both parents in 133 families, and from only the mother in 64 families. 117 of the ADHD probands had at least one sibling who was also genotyped. The Taiwanese sample consisted of 212 ADHD children. Both parents were available for 114 families, only the mother for 59 families and only the father for 39 families.
Sample Collection	Patients were collected from United Kingdom and Taiwan.
Diagnosis Description	For the United Kingdom sample, cases were referred for assessment if they were thought by experienced clinicians to have a diagnosis of the combined subtype of ADHD under DSM-IV criteria, with no significant Axis I co-morbidity apart from opposi- tional defiant disorder (ODD) and conduct disorder (CD) and IQ greater than 70. Parents were interviewed with a modified version of the Child and Adolescent Psychiatric Assessment (CAPA). Information on ADHD symptoms at school was obtained using the long form of the Conner's questionnaire. For the Taiwan sample, ADHD cases were ascertained from the Child Psychiatric Clinics in the Chang Gung Memorial Hospital in Taipei area, Taiwan. A diagnosis of ADHD was made according to DSM-IV criteria following completion of a standard maternal interview, and completion of parent and teacher Conner's revised rating scales. Autism cases were excluded from the study. No other neurological or behavioural disorders were identified.
Technique	The -67A/T (rs2975226) and -839C/T (rs2652511) polymorphisms were genotyped using PCR and enzyme digestion. For more detailed information, please refer to the original publication.
Analysis Method	Family genotype data were analysed using the transmission disequilibrium test (TDT) implemented in UNPHASED program (TDTPHASE). Linkage disequilibrium (LD) was estimated by calculating D' and r²statistics. The Bonferroni correction was applied for multiple comparisons and P-value<0.0125 was considered to show a statistically significant difference.
Result Description	TDT analysis showed that the T allele of the -67A/T polymorphism was significantly over-transmitted to affected probands in the Taiwanese population. Even after correcting p-values using the Bonferroni method for multiple comparisons a significant association was still found between the -67T allele and ADHD cases in Taiwanese population. No significant association was seen in the United Kingdom sample for this marker using either standard TDT analysis, or the extended TDT analysis including siblings, although the T-allele was over-transmitted (OR=1.16). A combined analysis including both population samples found significant association of the T-allele. No difference in the transmission of any alleles of the -839C/T polymorphism to ADHD was found in either of the two populations. Haplotype analysis revealed that the haplotype -67T/-839T was significantly over-transmitted to the Taiwanese ADHD probands and combined United Kingdom and Taiwanese samples, while haplotype -67A/-839T was significantly under-transmitted to Taiwanese ADHD probands and combined samples.

SNPs reported by this study (count: 2)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2975226	A/T		TDT: P-value=0.502 in UK sample; P-value=0.001 in Taiwanese sample; P-value=0.003 in combined sample.	significant association was found between this SNP and ADHD ...... significant association was found between this SNP and ADHD in Taiwanese population. More...	Significant
rs2652511	C/T		TDT: P-value=0.919 in UK sample; P-value=0.123 in Taiwanese sample; P-value=0315 in combined sample.	no significant association with ADHD was found no significant association with ADHD was found	Non-significant

Genes reported by this study (count: 1)