Circadian gene variants and susceptibility to type 2 diabetes: A pilot study

M. Ann Kelly, Simon D. Rees, Zafar L. Hydriem, A. Samad Shera, Srikanth Bellary, J. Paul O'Hare, Sudhesh Kumar, Shahrad Taheri, Abdul Basit, Anthony H. Barnett

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background: Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. Methodology/Principal Findings: The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66-0.86], p = 3.18×10-5), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07-1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01-1.08], p = 0.008 and OR = 0.95 [0.91-0.99], p = 0.015 respectively). Conclusions/significance: None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.

Original languageEnglish
Article numbere32670
JournalPloS one
Volume7
Issue number4
DOIs
Publication statusPublished - 2 Apr 2012

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Kelly, M. A., Rees, S. D., Hydriem, Z. L., Shera, A. S., Bellary, S., O'Hare, J. P., Kumar, S., Taheri, S., Basit, A., & Barnett, A. H. (2012). Circadian gene variants and susceptibility to type 2 diabetes: A pilot study. PloS one, 7(4), [e32670]. https://doi.org/10.1371/journal.pone.0032670