CDKAL1 and HHEX are associated with type 2 diabetes-related traits among Yup'ik people

Yann C. Klimentidis, Dominick J. Lemas, Howard H. Wiener, Diane M. O'Brien, Peter J. Havel, Kimber L. Stanhope, Scarlett E. Hopkins, Hemant K. Tiwari, Bert B. Boyer

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), mainly among individuals of European ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D-related traits in an Alaska Native study population with a historically low prevalence of T2D. We also investigated whether dietary characteristics that may protect against T2D, such as n-3 polyunsaturated fatty acid (PUFA) intake, modify these associations. Methods: In 1144 Yup'ik people, we examined 17 SNPs repeatedly identified in GWAS for individual and cumulative associations with T2D-related traits. Cumulative associations were evaluated using a genetic risk score (GRS) calculated by summing risk alleles. Associations were tested for interactions with sex, body mass index (BMI), and n-3 PUFA intake. Results: The rs7754840 SNP in CDKAL1 is significantly associated with HbA1c (P=0.00091). The rs5015480 SNP near HHEX is significantly associated (in opposite direction to that in Europeans) with a combined fasting glucose (FG) and HbA1c measure (P=0.00046) and with homeostatic model assessment of β-cell function (HOMA-B; P=0.0014). The GRS is significantly associated with FG and combined FG and HbA1c only when the HHEXSNP is dropped from the GRS. Associations are not modified by BMI or n-3 PUFA intake. Conclusion: Our results highlight the potential importance of CDKAL1 and HHEX in glucose homeostasis in this Alaska Native population with a low prevalence of T2D, and suggest that these loci should be examined in greater detail in this population.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalJournal of Diabetes
Issue number3
StatePublished - May 2014
Externally publishedYes


  • Alaska Native
  • Glycemic traits
  • N-3 polyunsaturated fatty acids
  • Type 2 diabetes single nucleotide polymorphisms

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


Dive into the research topics of 'CDKAL1 and HHEX are associated with type 2 diabetes-related traits among Yup'ik people'. Together they form a unique fingerprint.

Cite this