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Chunk #27 — Discussion

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Genetic variants in SLC9A9 are associated with measures of attention-deficit/hyperactivity disorder symptoms in families.
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shown that informant ratings are often discordant [reviewed in Ref. (De Los and Kazdin, 2005)]. Nonetheless, we are encouraged to find that rs1046706 showed nominal associations with hyperactive-impulsive, inattentive, and total symptom subscales according to the CPRS. Interestingly, this 3′UTR SNP does not seem to be tagging additional known SNPs and may itself be functionally relevant. However, verification of this would require experimental work that was not carried out in the present study. The 3′UTR sequence contains a variety of regulatory elements that may impact gene expression levels. MicroRNA binding sites are often located in the 3′UTR of genes and polymorphisms located within or near a microRNA-binding site are particularly good functional candidates for affecting gene expression. For example, a dihydrofolate reductase 3′UTR SNP that was located 14 bp away from a miR-24 binding site caused dihydrofolate reductase overexpression by interfering with the normal function of miR-24 (Mishra et al., 2007). In addition, the rate of mRNA decay is an important post-transcriptional mechanism, and can be influenced by both cis-elements found primarily in the 3′UTR and various RNA-binding proteins (Bolognani and Perrone-Bizzozero, 2008). Interestingly, these interactions which affect mRNA stability have recently been described in neurons (Bolognani and Perrone-Bizzozero, 2008).