Association of NRXN3 Deletion with Schizophrenia and Bipolar Disorder
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Background: Schizophrenia (SZ) and bipolar disorder (BD) are the most severe neuropsychiatric disorders affecting 1.2% and 4.4% of Americans, respectively. Certain genes coding for proteins involved in pre-synaptic machinery are thought to play a role in the pathophysiology of the disorder. Deficits in the calcium channel regulator gene NRXN3 have been associated with behaviors of impulsivity and alcohol and drug dependence, which are traits characteristic of BD and SZ. Methods: In this study, we performed a family based association analysis to determine if an 8KB deletion within the NRXN3 gene was associated with SZ, BD, or a combined phenotype using a TaqMan® Copy Number Assay (Thermo Fisher Scientific, Waltham, MA, USA) to target the region of interest within the NRXN3 gene, according to the manufacturer's recommendations. Reactions were run in quadruplicate with DNA concentrations normalized to the RNase P reference gene. The integer of each copy number was estimated using the CopyCaller software (Applied Biosystems, Foster City, CA, USA) in addition to standardized z scores and confidence values. Family based association testing was performed using the FBAT ver 2.0.4 software package for BD, SZ and combined phenotypes. Results: SZ, BD, or combined phenotypes were not significantly associated with the NRXN3 deletion (p-value> 0.05). Conclusions: Although we were unable to report a significant association between the NRXN3 deletion and BD, SZ, on combined phenotypes, a trend toward significance was seen in the BD (P=0.11) and combined phenotypes (P=0.13) most likely attributed to the BD phenotype.