Association of the KCNJ5 gene with Tourette Syndrome and Attention‐Deficit/Hyperactivity Disorder. (19th June 2014)

• Record Type: Journal Article
• Authors: Gomez, L.; Wigg, K.; Zhang, K.; Lopez, L.; Sandor, P.; Malone, M.; Barr, C. L.
• Is Part Of: Genes, brain, and behavior. Volume 13:Number 6(2014:Aug.)
• Page Start: 535
• Page End: 542
• Publication Date: 2014-06-19
• Subjects: Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12141
• Languages: English
• ISSNs: 1601-1848

Abstract

<abstract abstract-type="main" id="gbb12141-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="gbb12141-para-0001">Linkage and association of Tourette Syndrome (TS) and Attention‐Deficit/Hyperactivity Disorder (ADHD) have previously been reported in the 11q24 chromosomal region. To identify the risk gene within the region we studied the potassium inwardly‐rectifying channel J5 (<italic>KCNJ5</italic>) gene in a sample of 170 nuclear families with TS. We genotyped eight markers across the gene and observed biased transmission of haplotypes from parents to probands in this sample. We then tested these markers in an independent sample of 242 nuclear families with ADHD and found the same haplotype was significantly over transmitted to ADHD probands. Screening of the coding region of <italic>KCNJ5</italic> in 48 probands with TS did not identify any variation that could explain the association of the haplotype. We also genotyped two microsatellite markers, one in the promoter and the other in the 3′ region and found no evidence for association for either marker for TS, however, we found significant evidence for association with the 3′ repeat and ADHD. A small gene (<italic>c11orf45</italic>) of unknown function lies within the first intron of <italic>KCNJ5</italic> that is transcribed in the opposite orientation and this gene may regulate the expression of <italic>KCNJ5</italic>. We studied the correlation of the expression of <italic>KCNJ5</italic> and the antisense transcript in brain tissues from control individuals and found that the antisense transcript and the short <italic>KCNJ5</italic> isoform are co‐expressed in three brain regions. The results of this study indicate that <italic>KCNJ5</italic> is associated with TS and ADHD in our samples, however, the functional variant(s) remain to be identified.</p> </abstract>