Published in:
01-05-2015 | Article
Season-dependent associations of circadian rhythm-regulating loci (CRY1, CRY2 and MTNR1B) and glucose homeostasis: the GLACIER Study
Published in: Diabetologia | Issue 5/2015
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Aims/hypothesis
The association of single nucleotide polymorphisms (SNPs) proximal to CRY2 and MTNR1B with fasting glucose is well established. CRY1/2 and MTNR1B encode proteins that regulate circadian rhythmicity and influence energy metabolism. Here we tested whether season modified the relationship of these loci with blood glucose concentration.
Methods
SNPs rs8192440 (CRY1), rs11605924 (CRY2) and rs10830963 (MTNR1B) were genotyped in a prospective cohort study from northern Sweden (n = 16,499). The number of hours of daylight exposure during the year ranged from 4.5 to 22 h daily. Owing to the non-linear distribution of daylight throughout the year, season was dichotomised based on the vernal and autumnal equinoxes. Effect modification was assessed using linear regression models fitted with a SNP × season interaction term, marginal effect terms and putative confounding variables, with fasting or 2 h glucose concentrations as outcomes.
Results
The rs8192440 (CRY1) variant was only associated with fasting glucose among participants (n = 2,318) examined during the light season (β = −0.04 mmol/l per A allele, 95% CI −0.08, −0.01, p = 0.02, p
interaction = 0.01). In addition to the established association with fasting glucose, the rs11605924 (CRY2) and rs10830963 (MTNR1B) loci were associated with 2 h glucose concentrations (β = 0.07 mmol/l per A allele, 95% CI 0.03, 0.12, p = 0.0008, n = 9,605, and β = −0.11 mmol/l per G allele, 95% CI −0.15, −0.06, p < 0.0001, n = 9,517, respectively), but only in participants examined during the dark season (p
interaction = 0.006 and 0.04, respectively). Repeated measures analyses including data collected 10 years after baseline (n = 3,500) confirmed the results for the CRY1 locus (p
interaction = 0.01).
Conclusions/interpretation
In summary, these observations suggest a biologically plausible season-dependent association between SNPs at CRY1, CRY2 and MTNR1B and glucose homeostasis.