Study Report

Basic Info
Reference |
Brookes KJ, 2008(b)18937300
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Citation |
Brookes K. J., Hawi Z., Kirley A., Barry E., Gill M. and Kent L. (2008) "Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1531-5.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
387 probands and their parents |
Predominant Ethnicity |
Caucasian |
Population |
United Kingdom, Ireland |
Gender |
male 88.3% |
Age Group |
Children/Adolescents
:
4-15 years
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Detail Info
Summary |
In this study they present evidence for a role of the X-linked steroid sulfatase (STS) gene and neurosteroids in the development of ADHD. In a moderately sized sample of ADHD families (N=384), they genotyped seven single nucleotide polymorphisms, tagging the entire gene. TDT analysis of the data yielded two polymorphisms that were significantly associated with ADHD (rs2770112-Transmitted: 71 Not Transmitted; 48; rs12861247-Transmitted: 43 Not Transmitted: 21), located towards the 5' end of the gene (P-value<0.05). They conclude that the STS gene may play a role in susceptibility for ADHD, and that the neurosteroids pathways should be investigated further to access their potential contribution in susceptibility to the disorder. |
Total Sample |
387 ADHD probands (inclusive of four affected siblings) and their parents were recruited from several child psychiatry clinics in the United Kingdom (N=115) and Ireland (N=272) |
Sample Collection |
white and born in the United Kingdom or Ireland |
Diagnosis Description |
All probands fulfilled DSM-IV diagnostic criteria for Attention Deficit Hyperactivity Disorder (ADHD). Of these N=318 (82.2%) had ADHD combined type, N=33 (8.5%) had the inattentive subtype, and N=36 (9.3%) had the hyperactive impulsive subtype. |
Technique |
High molecular weight genomic DNA was extracted from either whole blood or cheek swab according to routine procedures. Tagging SNPs were identified using genotype information from the HapMap Project and the Tagger program. Predesigned SNP genotyping assays were obtained from Applied Biosystems for use on the TaqMan 7300HT PCR realtime machine following a standardized protocol provided with the assays. |
Analysis Method |
TDT analysis of the sample was carried out using the program software UNPHASED; a subsequent conservative Bonferroni Correction applied for the number of markers investigated to any statistically significant results. In addition the UNPHASED program allows for permutations of the data. |
Result Description |
two polymorphisms that were significantly associated with ADHD and the STS gene may play a role in susceptibility for ADHD |

SNPs reported by this study (count: 7)
SNP |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
rs12861247 |
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TDT P-value=0.0055, OR=2.05; Bonferroni correction P-value=0.0385; P-value=0.015 for males only |
remains significant after correction; significantly associat......
remains significant after correction; significantly associated with male probands
More...
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Significant
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rs17268988 |
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TDT P-value=0.41, OR=1.18 |
not significantly associated
not significantly associated
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Non-significant
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rs2270112 |
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TDT P-value=0.034, OR=1.48 |
significantly associated
significantly associated
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Significant
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rs4403552 |
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TDT P-value=0.71, OR=1.07 |
not significantly associated
not significantly associated
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Non-significant
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rs5933863 |
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TDT P-value=0.28, OR=1.26 |
not significantly associated
not significantly associated
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Non-significant
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rs5934740 |
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TDT P-value=0.41, OR=1.15 |
not significantly associated
not significantly associated
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Non-significant
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rs7058445 |
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TDT P-value=0.32, OR=1.2 |
not significantly associated
not significantly associated
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Non-significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
STS |
STS global P-value=0.039; haplotype-specific P-value=0.03, O......
STS global P-value=0.039; haplotype-specific P-value=0.03, OR=1.52; support the hypothesis that the STS gene is a potential candidate for ADHD susceptibility
More...
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Significant
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