Discordant association of the CREBRF rs373863828 A allele with increased BMI and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand

Diabetologia. 2018 Jul;61(7):1603-1613. doi: 10.1007/s00125-018-4623-1. Epub 2018 May 2.

Abstract

Aims/hypothesis: The A (minor) allele of CREBRF rs373863828 has been associated with increased BMI and reduced risk of type 2 diabetes in the Samoan populations of Samoa and American Samoa. Our aim was to test rs373863828 for associations with BMI and the odds of type 2 diabetes, gout and chronic kidney disease (CKD) in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand.

Methods: Linear and logistic regression models were used to analyse the association of the A allele of CREBRF rs373863828 with BMI, log-transformed BMI, waist circumference, type 2 diabetes, gout and CKD in 2286 adults. The primary analyses were adjusted for age, sex, the first four genome-wide principal components and (where appropriate) BMI, waist circumference and type 2 diabetes. The primary analysis was conducted in ancestrally defined groups and association effects were combined using meta-analysis.

Results: For the A allele of rs373863828, the effect size was 0.038 (95% CI 0.022, 0.055, p = 4.8 × 10-6) for log-transformed BMI, with OR 0.59 (95% CI 0.47, 0.73, p = 1.9 × 10-6) for type 2 diabetes. There was no evidence for an association of genotype with variance in BMI (p = 0.13), and nor was there evidence for associations with serum urate (β = 0.012 mmol/l, pcorrected = 0.10), gout (OR 1.00, p = 0.98) or CKD (OR 0.91, p = 0.59).

Conclusions/interpretation: Our results in New Zealand Polynesian adults replicate, with very similar effect sizes, the association of the A allele of rs373863828 with higher BMI but lower odds of type 2 diabetes among Samoan adults living in Samoa and American Samoa.

Keywords: Association; BMI; CREBRF; Genetic; Māori; Obesity; Pacific; Polynesian; Type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • New Zealand / epidemiology
  • Obesity / diagnosis
  • Obesity / ethnology
  • Obesity / genetics*
  • Oceanic Ancestry Group / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Polynesia / ethnology
  • Protective Factors
  • Risk Factors
  • Tumor Suppressor Proteins / genetics*

Substances

  • CREB3 regulatory factor, human
  • Tumor Suppressor Proteins