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Circadian clock genes are critical regulators of energy homeostasis and metabolism. However, whether variation in the circadian genes is associated with metabolic phenotypes in humans remains to be explored. In this study, we systemically genotyped 20 tag single nucleotide polymorphisms (SNPs) in 8 candidate genes involved in circadian clock, including  CLOCK ,  BMAL1 ( ARNTL ),  PER1 ,  PER2 ,  CRY1 ,  CRY2 ,  CSNK1E, , and  NOC ( CCRN4L ) in 1,510 non-diabetic Chinese subjects in Taipei and Yunlin populations in Taiwan. Their associations with metabolic phenotypes were analyzed. We found that genetic variation in the  NOC  gene, rs9684900 was associated with body mass index (BMI) ( P  = 0.0016, Bonferroni corrected  P  = 0.032). Another variant, rs135764 in the  CSNK1E  gene was associated with fasting glucose ( P  = 0.0023, Bonferroni corrected  P  = 0.046). These associations were consistent in both Taipei and Yunlin populations. Significant epistatic and joint effects between SNPs on BMI and related phenotypes were observed. Furthermore,  NOC  mRNA levels in human abdominal adipose tissue were significantly increased in obese subjects compared to non-obese controls.    Conclusion  Genetic variation in the  NOC  gene is associated with BMI in Chinese subjects.

Genetic Variation in the NOC Gene Is Associated with Body Mass Index in Chinese Subjects