Association of schizophrenia with the phenylthiocarbamide taste receptor haplotype on chromosome 7q

Abstract

Phenylthiocarbamide (PTC) taste sensitivity is an inherited trait determined primarily by allelic variation of the taste-receptor gene TAS2R38 on chromosome 7q. Results of prior studies examining the ability to taste PTC in patients with schizophrenia have been mixed because of the difficulties in measuring PTC taste sensitivity behaviorally. In the current study, we examined the TAS2R38 genotypes of schizophrenia patients to determine whether the increased prevalence of nontasters in this patient population was indicative of a specific genetic association. Our a-priori hypothesis was that schizophrenia patients would show an increased prevalence of the nontaster phenotype compared with controls. The genotypes of two nonsynonymous coding single-nucleotide polymorphisms in TAS2R38 were assayed for 176 schizophrenia patients and 229 healthy control individuals, and the two-allele haplotypes were estimated. There was an over-representation of the major PTC nontaster haplotype among patients of European descent, relative to control individuals of similar ancestry. Patients and controls of African ancestry did not differ. The PTC nontaster haplotype is a genetic marker that may be used to identify subsets of schizophrenia patients who potentially harbor vulnerability genes in this region of chromosome 7q.

Gene set enrichment analysis of RNA-Seq data: integrating differential expression and splicing

“…Interestingly, with a high weight on DS, two gene sets regarding taste perception were detected. Evidence also has shown that taste-blindness is highly associated with schizophrenia [38,39], but more importantly, our analysis suggested that this association was largely formulated through the regulation of alternative splicing. The full results on BA46 with analysis are available in Supplementary Table S5, and those for the cancer data are in Supplementary Tables S6-S7.…”

An alternative laboratory designed to address ethical concerns associated with traditional TAS2R38 student genotyping

“…In this case, one could make genotype/phenotype assignments based on the findings of Lee and colleagues, such that students assigned T785‐containing genotypes would predominantly be assigned the phenotype of P. aeruginosa associated sinus infection . Alternatively, labs could be designed using other published phenotypes associated with TAS2R38 variants, such as schizophrenia or colorectal cancer . Finally, if instructors prefer that students meet the learning objective of working with authentic, student‐produced data and they are comfortable dispensing with the human DNA testing learning objective, a variety of alternative labs could be implemented .…”

“…This association was not seen in a more recent study, but the study did not have sufficient statistical power to detect a possible association in the Caucasian population [6]. A 2012 study claimed that TAS2R38 genotype is associated with an increased risk of schizophrenia, but scientific evidence regarding this association has been controversial [7,8]. A new study proposes a role for the T2R family of receptors, including T2R38, in off target effects of pharmaceuticals [9].…”