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	Brookes KJ, 201020862695
Citation	Brookes K. J., Hawi Z., Park J., Scott S., Gill M. and Kent L. (2010) "Polymorphisms of the steroid sulfatase (STS) gene are associated with attention deficit hyperactivity disorder and influence brain tissue mRNA expression." Am J Med Genet B Neuropsychiatr Genet, 153B(8): 1417-24.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	450 ADHD probands and their parents
Predominant Ethnicity	Caucasian
Population	United Kingdom, Ireland
Gender	male (90.1%)
Age Group	Children/Adolescents : 4-16 years

Detail Info

Summary	This family based association study has fine mapped a region of the STS gene across intron 1 and 2 previously associated with ADHD, in an extended sample of 450 ADHD probands and their parents. Significant association across this region is demonstrated individually with 7 of the 12 genotyped SNPs, as well as an allele specific haplotype of the 12 SNPs. The over transmitted risk allele of rs12861247 was also associated with reduced STS mRNA expression in normal human post-mortem frontal cortex brain tissue compared to the non-risk allele (P-value=0.01). These results are consistent with the hypothesis arising from previous literature demonstrating that boys with deletions of the STS gene, and hence no STS protein are at a significantly increased risk of developing ADHD. Furthermore, this study has established the brain tissue transcript of STS, which except from adipose tissue, differs from that seen in all other tissues investigated.
Total Sample	450 ADHD probands (inclusive of 12 affected siblings) and their parents were recruited from several child psychiatry clinics in the United Kingdom (N=183) and Ireland (N=267).
Sample Collection	White and born in the United Kingdom or Ireland
Diagnosis Description	all probands fulfilled DSM-IV diagnostic criteria for ADHD. N=42 (9.3%) had the inattentive subtype, and N=38 (8.4%) had the hyperactive impulsive subtype, the rest had combined subtype (82.3%). Children with an IQ below 70, autistic spectrum disorder or significant medical conditions such as epilepsy were excluded. Two-hundred eleven children (46.9%) had comorbid oppositional defiant disorder and 69 children (15.3%) fulfilled criteria for comorbid conduct disorder.
Technique	Association Study and Brain sample Genotyping; Alternative First Exon Genotyping; DNA Sequencing; mRNA Expression
Analysis Method	TDT analysis and some correction for multiple testing using the program software UNPHASED. Linkage disequilibrium across the SNPs and haplotype analysis were performed in Haploview.
Result Description	Novel findings for five SNPs in this region were found with significant evidence for association: rs6639786, rs5934769, rs5934770 located within intron 1; rs17335568 located within intron 2; and rs1473666 in the alternate exon (0b) located upstream in the 50 region of 5HD1A1A. Two of the previously genotyped SNPs, rs2270112 and rs12861247 were also still significant in this larger sample. However, none survived stringent correction for multiple testing and 1,000 permutations of the data provided a trend for significance only.

SNPs reported by this study (count: 12)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs5934769			TDT P-value=0.03, OR=1.20	significant evidence for association, but cannot survive str...... significant evidence for association, but cannot survive stringent correction for multiple testing More...	Significant
rs5934770			TDT P-value=0.02, OR=1.25	significant evidence for association, but cannot survive str...... significant evidence for association, but cannot survive stringent correction for multiple testing More...	Significant
rs6639786			TDT P-value=0.01, OR=1.26	significant evidence for association, but cannot survive str...... significant evidence for association, but cannot survive stringent correction for multiple testing More...	Significant
rs7058445			TDT P-value=0.68, OR=1.14	no significant association no significant association	Non-significant
rs1473666			TDT P-value=0.05, OR=1.17	significant evidence for association, but cannot survive str...... significant evidence for association, but cannot survive stringent correction for multiple testing More...	Non-significant
rs12861247			TDT P-value=0.01, OR=1.88	was previously genotyped and still significant in this large...... was previously genotyped and still significant in this larger sample but cannot survive stringent correction for multiple testing; also associated with reduced STS mRNA expression in normal human post-mortem frontal cortex brain tissue compared to the non-risk allele (P-value=0.01) More...	Significant
rs11095437			TDT P-value=0.36, OR=1.23	no significant association no significant association	Non-significant
rs1000900			TDT P-value=0.70, OR=1.14	no significant association no significant association	Non-significant
rs5934740			TDT P-value=0.33, OR=1.07	no significant association no significant association	Non-significant
rs2270112			TDT P-value=0.03, OR=1.31	was previously genotyped and still significant in this large...... was previously genotyped and still significant in this larger sample but cannot survive stringent correction for multiple testing More...	Significant
rs2024159			TDT P-value=1.00, OR=1.08	no significant association no significant association	Non-significant
rs17335568			TDT P-value=0.01, OR=1.27	significant evidence for association, but cannot survive str...... significant evidence for association, but cannot survive stringent correction for multiple testing More...	Significant

Genes reported by this study (count: 1)