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(a)19416518
Citation	Xu X., Brookes K., Sun B., Ilott N. and Asherson P. (2009) "Investigation of the serotonin 2C receptor gene in attention deficit hyperactivity disorder in UK samples." BMC Res Notes, 2: 71.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	180 families
Predominant Ethnicity	Caucasian
Population	United Kingdom
Gender	96% of the sample was male
Age Group	Children/Adolescents : aged 5-15 years old, mean age 10.41 years (SD=2.34)

Detail Info

Summary	This study investigated the association between ADHD and two polymorphisms C-759T (rs3813929) and G-697C (rs518147) in the promoter region of the HTR2C gene using a sample of 180 United Kingdom ADHD probands and their parents. It has shown that the -697G allele was significantly over-transmitted to affected ADHD probands (P-value=0.017). No association was detected between the C-759T polymorphism and ADHD. Haplotype analysis of the two markers revealed no significantly increased transmission of any haplotype to ADHD. The findings provide evidence that the G-allele of the G-697C HTR2C polymorphism may be involved in the development of ADHD.
Total Sample	Patients were composed of 180 DSM-IV ADHD combined subtype probands, from both parents for 116 of the ADHD probands and from the mother alone for 64 of the probands.
Sample Collection	All ADHD patients were from United Kingdom
Diagnosis Description	Cases were recruited from child behaviour clinics in South-East United Kingdom and 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 oppositional defiant disorder (ODD) and conduct disorder (CD) and IQ greater than 70. Only those individuals fulfilling the recruitment criteria after completion of research assessments were included in the study. 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.
Technique	The C-759T (rs3813929) and G-697C (rs518147) polymorphisms were genotyped using the method of PCR and enzyme digestion. The reaction was performed according to the protocol described in the previous study. 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). Since HTR2C is X-linked gene, genotype data from fathers was only used in the analysis of female ADHD probands. Genotype information from both parents in female probands, and from mothers alone in male probands was used to analyse linkage disequilibrium (LD). The Bonferroni correction was applied for multiple tests and P-value<0.025 was considered to show a statistically significant difference.
Result Description	TDT analysis showed that the -697G allele was significantly over-transmitted to affected probands. Even after correcting p-values using the Bonferroni method for multiple tests a significant association was still found between the -697G allele and ADHD. Nevertheless, this finding should be treated with caution until further replication studies have been completed, since the significance level falls far below that required to adjust for the number of independent genetic variants across the genome. No difference in the transmission of any alleles of the C-759T SNP to ADHD was found. Moderate LD was observed between the HTR2C markers (D'=0.63). Haplotype analysis of the two markers revealed no significantly increased transmission of any haplotype to ADHD.

SNPs reported by this study (count: 2)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs518147	G-697C		TDT P-value=0.017, OR=1.7	significantly associated with ADHD, even after correcting P-...... significantly associated with ADHD, even after correcting P-values using the Bonferroni method for multiple tests. More...	Significant
rs3813929	C-759T		TDT P-value=0.384, OR=1.2	no significant association with ADHD was found no significant association with ADHD was found	Non-significant

Genes reported by this study (count: 1)