Role of polygenic risk scores in the association between chronotype and health risk behaviors

Abstract

Background: This study explores the association between chronotypes and adolescent health risk behaviors (HRBs) by testing how genetic background moderates these associations and clarifies the influence of chronotypes and polygenic risk score (PRS) on adolescent HRBs.

Methods: Using VOS-viewer software to select the corresponding data, this study used knowledge domain mapping to identify and develop the research direction with respect to adolescent risk factor type. Next, DNA samples from 264 students were collected for low-depth whole-genome sequencing. The sequencing detected HRB risk loci, 49 single nucleotide polymorphisms based to significant SNP. Subsequently, PRSs were assessed and divided into low, moderate, and high genetic risk according to the tertiles and chronotypes and interaction models were constructed to evaluate the association of interaction effect and clustering of adolescent HRBs. The chronotypes and the association between CLOCK-PRS and HRBs were examined to explore the association between chronotypes and mental health and circadian CLOCK-PRS and HRBs.

Results: Four prominent areas were displayed by clustering information fields in network and density visualization modes in VOS-viewer. The total score of evening chronotypes correlated with high-level clustering of HRBs in adolescents, co-occurrence, and mental health, and the difference was statistically significant. After controlling covariates, the results remained consistent. Three-way interactions between chronotype, age, and mental health were observed, and the differences were statistically significant. CLOCK-PRS was constructed to identify genetic susceptibility to the clustering of HRBs. The interaction of evening chronotypes and high genetic risk CLOCK-PRS was positively correlated with high-level clustering of HRBs and HRB co-occurrence in adolescents, and the difference was statistically significant. The interaction between the sub-dimensions of evening chronotypes and the high genetic CLOCK-PRS risk correlated with the outcome of the clustering of HRBs and HRB co-occurrence.

Conclusions: The interaction of PRS and chronotype and the HRBs in adolescents appear to have an association, and the three-way interaction between the CLOCK-PRS, chronotype, and mental health plays important roles for HRBs in adolescents.

Keywords: CLOCK-PRS; Chronotype; Gene-environment; Health risk behaviors.