Validation and TaqMan Conversion of a Molecular Chronotype Assessment Approach.

Abstract

The present study aimed to develop a TaqMan genotyping card for molecular chronotype assessment based on a predictive panel of 35 previously identified genetic variants. A reliable TaqMan assay was successfully developed for 33 out of the 35 chronotype-predictive variants. The resulting TaqMan genotyping card was utilized to genetically characterize 196 new individuals (in addition to the previously studied 96) and the Morningness-Eveningness Questionnaire was utilized for their phenotypical chronotype assessment. The predictive panel performance was validated on (a) a group of morning and evening individuals (logistic regression model), (b) a representative sample of the original study population also including intermediate chronotypes (linear regression model) and, (c) 25,986 individuals from the Estonian Biobank, for whom Munich Chronotype Questionnaire scores were available. The validation of the morningness-eveningness logistic regression model on 25 morning and 21 evening types resulted in a predictive value of 72%, confirming the reliability of the predictive panel and the success of its conversion into a TaqMan genotyping card. By contrast, the inclusion of intermediate individuals in the model led to a significant decrease in predictive performance (45% on 100 individuals [25 morning, 54 intermediate, and 21 evening]), with intermediate types being the most affected. No significant associations were observed between the genotype panel and chronotype in the Estonian Biobank sample. In conclusion, our genotyping card might represent a promising molecular chronotyping tool for the Italian population. Its performance in other populations is worthy of further study.