Pathway-based analysis of genome-wide association study of circadian phenotypes

Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms(SNPs) which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies(GWAS) dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype-phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime,totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration.

Diurnal Circadian Lighting Accumulation Model:A Predictor of the Human Circadian Phase Shift Phenotype

Light is an important external factor that affects human circadian rhythms.This study aimed to explore the effects of different dimensions of diurnal light exposure on the physiological circadian phase shift(CPS)of the human body.A strict light exposure experiment with different timing schemes(8:00-12:00,13:00-17:00,18:00-22:00),durations(4 h,8 h)and effective circadian stimulus levels(circadian stimulus:0.35,0.55)was performed in an enclosed laboratory.Fourteen participants,including seven males and seven females,with a mean age of 24.29±2.43(mean±standard deviation),participated in this experiment and experienced all six lighting schemes.The results showed that both time factor(F_(3,40)=29.079,p<0.001,the power of the sample size=0.98)and circadian stimulus levels(T_(20)=−2.415,p=0.025,the power of sample size=0.76)sig-nificantly affect the CPS.On this basis,a diurnal circadian lighting accumulation(DCLA)-CPS model was proposed in the form of the Boltzmann function,and was validated by experimental data with high correlation(R^(2)=0.9320,RSS=0.1184),which provides strong support for rationally arranging the light level at different times of the day.