The aim of this study was to assess the role of clock in eating patterns and associated metabolic cytokines. The 1100 participants recruited from the Genetics of Lipid Lowering Drugs and Diet Network cohort were genotyped, filled out the Diet History Questionnaire, and gave blood samples for cytokine analysis.
It was determined that after adjusting for several confounders, carriers the minor alleles inclock SNPs rs3749474 and rs4580704 had lower and higher dietary energy intake respectively.
Additionally, rs3749474 was associated with the inflammatory cytokine monocyte chemotactic protein 1. Other associations were nominally significant, but were no longer significant after Bonferroni adjustment for multiple testing.
SNPs in clock
To test the hypothsis that polymorphisms in clock genes affect weight and the likelihood of binge eating disorder, 192 overweight/obese people and 92 age and sex matched normal weight controls were recruited for a case control study. They were genotyped for the rs1801260 SNP in clock, had their BMIs measured, and were assessed for Binge Eating Disorder by the Structured Clinical Interview.
The authors found no significant difference between genotype or allele frequency and obesity, even after statifying the patients by binge eating status. However, within the overweight/obese group, it was determined that the CC genotype and C allele of rs1801260 were associated with higher BMI (40kg/m²) compared to other geotypes and the T allele.
rs1801260 in clock
NCBI Variation Viewer rs1801260
To determine the association between SNPs in circadian genes and sleep disturbances in the elderly, data was analyzed from 2 different cohort studies; the Study of Osteoporotic Fractures (SOF) and Osteoporotic Fractures in Men (MrOS). Participants were aged 65 or older, were genotyped and had their activity measured via wrist-mounted actigraphs.
It was determined that several SNPs were associated with many characteristics of sleep. In a meta analysis of both studies, rs1047776 in leprel2 and rs2238114 in usp5 are associated with wake after sleep onset, a measure of sleep quality. In the MrOS study, rs3816358 in bmal1, rs3768984 in npas2, and their interaction were found to be associated with sleep and wake timing. Finally, the SOF analysis found that rs895520 in npas2 and rs1047776 in leprel2 were associated with activity robustness and sleep latency respectively.
rs1047776 in leprel2
NCBI Variation Viewer rs1047776
rs2238114 in usp5
NCBI Variation Viewer rs2238114
rs3816358 in bmal1
NCBI Variation Viewer rs3816358
rs3768984 and rs895520 in npas2
NCBI Variation Viewer rs3768984-rs895520
To elucidate the role of circadian SNPs in bipolar disorder (BD), a study in which 39 inpatients with DSV-IV diagnosed BD was performed. The subjects had their activity measured by wrist actigraphs and were genotyped for the rs1801260 SNP in clock.
It was determined that the carriers of the C allele of rs1801260 had higher activity at night, and that the effect of lithium on activity was mediated by genotype. These results, while statistically significant, were not adjusted for the multiple tests that were performed and may thus be false positives.
rs1801260 in clock
NCBI Variation Viewer rs1801260
In order to determine the role of SNPs in circadian genes in breast cancer, and whether these SNPs could mediate the effect of night shift work on risk of cancer, a case-control study was performed in which French women aged 25-75 with (n=1126) and without (n=1174) breast cancer gave buccal or blood samples. Participants were also interviewed to determine demographic, lifestyle, medical, and work history information.
In an analysis of 577 SNPs in circadian genes, rs1482057 and rs12914272 in ror-a were found to be associated with breast cancer after adjustment for several confounding variables and multiple testing. In post-menopausal women, these SNPs and rs11932595 in clock were found to be very nearly significantly associated with breast cancer, after adjustment. Tests for interaction between night shift work and SNPs were not significant after FDR post-hoc procedures
Additionally, a whole-gene analysis of SNPs found that the circadian pathway and clock in particular were significantly associated with breast cancer only in post-menopausal women.
SNPs in ror-a
NCBI Variation Viewer rs1482057-rs12914272
To assess the contribution of SNPs in Clock genes, the authors analyzed the data from 819 paarticipants of the Genetics of Lipid Lowering Drugs and Diet Network Study. Blood pressure and samples for genotyping were taken from each analyzed participant.
Using the Genome-Wide Complex Trait Analysis to assess the combined effect of 5004 SNPs in clock genes, the authors found that clock genes explained 7.1±3% of the total variability in systolic blood pressure. The genes were not found to be significantly associated with diastolic blood pressure, and an analysis of each SNP separately found no significant associations after correcting for multiple testing, and a replication study confirmed this result.