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Toward a Molecular Approach to Chronotype Assessment
Alberto Biscontin1, Lisa Zarantonello1, Antonella Russo2
1Department of Medicine, University of Padova, Padova, Italy.
Journal of Biological Rhythms
|May 18, 2022
Summary
This study developed a Polygenic Score model to predict molecular chronotype using genetic variants. The model, utilizing 35 or 13 single-nucleotide polymorphisms (SNPs), achieved 80% predictive accuracy for chronotype.
Area of Science:
- Genetics
- Chronobiology
- Sleep Science
Background:
- Chronotype, an individual's daily biological rhythm, influences sleep-wake patterns and behavior.
- Current chronotype assessment relies on questionnaires, which can be subjective.
- Genetic factors play a significant role in determining an individual's chronotype.
Purpose of the Study:
- To develop a Polygenic Score (PGS)-based model for objective molecular chronotype assessment.
- To identify novel genetic variants associated with chronotype.
- To create genetic panels for chronotype prediction.
Main Methods:
- Genotyping by sequencing of 19 circadian rhythm-related genes in individuals with extreme morning/evening chronotypes.
- Utilized single primer enrichment technology and a custom primer panel.
- Applied a cross-validation approach to identify predictive genetic variants (SNPs).
Main Results:
- Identified 83 chronotype-predictive variants, including novel polymorphisms.
- Developed two panels of SNPs (35 and 13 SNPs) with approximately 80% predictive validity for chronotype.
- Formulated hypotheses for the mechanistic roles of newly identified variants.
Conclusions:
- A PGS-based model shows promise for accurate molecular chronotype assessment.
- The identified SNP panels could be valuable for circadian public health and precision medicine.
- Further validation in diverse populations is needed to confirm utility.
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