Abstract
Previous studies in animals and humans have implicated the X-chromosome STS gene in the etiology of attentional difficulties and attention deficit hyperactivity disorder (ADHD). 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 = 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. © 2010 Wiley-Liss, Inc.
Highlights
Attention deficit hyperactivity disorder (ADHD) is one of the most heritable and prevalent childhood psychiatric disorders [Asherson, 2004], affecting an estimated 5% of school-aged children [Polanczyk et al, 2007]
Like most other neurobehavioral disorders, ADHD presents with a male bias [Swanson et al, 1998], which supports a possible role for X-linked genes in the etiology
Boys with X-linked ichthyosis, who have a deletion or point mutation of STS are at an increased risk of ADHD [Kent et al, 2008] and common variants within the STS gene may increase susceptibility to ADHD [Brookes et al, 2008]
Summary
Attention deficit hyperactivity disorder (ADHD) is one of the most heritable and prevalent childhood psychiatric disorders [Asherson, 2004], affecting an estimated 5% of school-aged children [Polanczyk et al, 2007]. Like most other neurobehavioral disorders, ADHD presents with a male bias [Swanson et al, 1998], which supports a possible role for X-linked genes in the etiology Recent work from both human and animal studies suggests the X-linked gene; steroid sulfatase (STS) may have a role in attention. Boys with X-linked ichthyosis, who have a deletion or point mutation of STS are at an increased risk of ADHD [Kent et al, 2008] and common variants within the STS gene may increase susceptibility to ADHD [Brookes et al, 2008]. Both pharmacological manipulation of the steroid sulfatase axis and haplo-insuffi-.
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