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

Detail ...

Study Report

Basic Info

Reference	Sengupta, S. M., 201222297068
Citation	Sengupta S. M., Grizenko N., Thakur G. A., Bellingham J., DeGuzman R., Robinson S., TerStepanian M., Poloskia A., Shaheen S. M., Fortier M. E., Choudhry Z. and Joober R. (2012) "Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype." J Psychiatry Neurosci, 37(2): 129-37.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	380 nuclear families with 412 ADHD children
Predominant Ethnicity	Caucasian
Population	Canadian
Gender	78.3% were boys
Age Group	Children/Adolescents : mean age of participants was 9 (standard deviation [SD] 1.8)

Detail Info

Summary	Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT. RESULTS: A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplo-type block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2.
Total Sample	The study included 380 nuclear families having at least 1 child with a DSM-IV diagnosis of ADHD. Of the 380 families, 184 were trios with information from both parents, 18 were trios with 2 affected children, 49 were trios with in - formation from 1 parent and 1 or more unaffected siblings, 115 were duos including the proband and 1 parent, and 14 were families with 2 affected siblings and 1 parent. A total of 412 children with ADHD were included in the study. 53.2% met DSM-IV criteria for the combined subtype, whereas 36.7% and 10.1% met the criteria for the inattentive and hyperactive subtypes, respectively.
Sample Collection	Children between 6 and 12 years of age with a diagnosis of ADHD were recruited from the Disruptive Behaviour Disorders Program and the child psychiatry outpatient clinics at the Douglas Mental Health University Institute in Montreal, Canada.
Diagnosis Description	Each child received a diagnosis of ADHD based on DSM-IV criteria. In addition to the DSM-IV diagnosis of ADHD, the behaviour of the child was used as a quantitative trait in the genetic analysis.
Technique	The tag SNPs within NET that had previously been examined in the IMAGE project were genotyped. The panel of SNPs was genotyped using Sequenom iPlex Gold Technology.
Analysis Method	Family-based association tests (examining transmission disequilibrium of a specific allele/haplotype from parent to affected offspring) were conducted using the FBAT statistical software package (version 2.0.3).
Result Description	A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplo-type block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2. LIMITATIONS: The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype. The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples.

SNPs reported by this study (count: 30)

SNP	Allele Change	Statistical Values	Author Comments	Result of Statistical Analysis
rs28386840	A/T	P-value=0.48, Z statistic (allele 1)=0.71	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs1814269	G/A	P-value=0.1, Z statistic (allele 1)=¨C1.66	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs36017	C/G	P-value=0.13, Z statistic (allele 1)=¨C1.53	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs36021	T/A	P-value=0.008, Z statistic (allele 1)=2.64	Two of the SNPs (rs3785143 and rs36021) showed a significant...... Two of the SNPs (rs3785143 and rs36021) showed a significant association with ADHD. More...	Significant
rs3785152	C/T	P-value=0.14, Z statistic (allele 1)=1.46	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs187714	T/C	P-value=0.12, Z statistic (allele 1)=¨C1.55	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs36023	C/T	P-value=0.56, Z statistic (allele 1)=0.58	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs187715	A/G	P-value=0.54, Z statistic (allele 1)=0.61	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs36024	C/T	P-value=0.18, Z statistic (allele 1)=1.33	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs192303	G/C	P-value=0.27, Z statistic (allele 1)=1.11	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs41154	A/G	P-value=0.08, Z statistic (allele 1)=¨C1.76	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs2242446	T/C	P-value=0.34, Z statistic (allele 1)=0.95	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs3785143	C/T	P-value=0.024, Z statistic (allele 1)=2.25	Two of the SNPs (rs3785143 and rs36021) showed a significant...... Two of the SNPs (rs3785143 and rs36021) showed a significant association with ADHD. More...	Significant
rs2397771	G/C	P-value=0.06, Z statistic (allele 1)=1.85	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs168924	T/C	P-value=0.68, Z statistic (allele 1)=0.41	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs4783899	G/T	P-value=0.09, Z statistic (allele 1)=¨C1.69	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs1362621	A/G	P-value=0.26, Z statistic (allele 1)=1.13	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs7188230	A/G	P-value=0.4, Z statistic (allele 1)=0.84	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs15534	C/T	P-value=0.45, Z statistic (allele 1)=0.76	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs2242447	T/C	P-value=0.25, Z statistic (allele 1)=1.15	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs1800887	T/C	P-value=0.25, Z statistic (allele 1)=1.16	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs36009	G/A	P-value=0.44, Z statistic (allele 1)=0.77	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs998424	C/T	P-value=0.08, Z statistic (allele 1)=1.76	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs5569	C/T	P-value=0.08, Z statistic (allele 1)=1.72	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs8047672	G/A	P-value=0.94, Z statistic (allele 1)=¨C0.08	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs2279805	T/C	P-value=0.15, Z statistic (allele 1)=¨C1.43	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs11568324	C/T	P-value=0.56, Z statistic (allele 1)=0.58	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs5564	T/C	P-value=0.2, Z statistic (allele 1)=1.27	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs3785155	G/A	P-value=0.98, Z statistic (allele 1)=0.03	No significant association was found in this study. No significant association was found in this study.	Non-significant
rs10521329	C/A	P-value> 0.99 , Z statistic (allele 1)=0	No significant association was found in this study. No significant association was found in this study.	Non-significant

Genes reported by this study (count: 1)