School of Medicine Publications and Presentations

Document Type

Article

Publication Date

9-2019

Abstract

Aims hypothesis

Variants in CREBRF (rs12513649 and rs373863828) have been strongly associated with increased BMI and decreased risk of type 2 diabetes in Polynesian populations; the A allele at rs373863828 is common in Polynesians but rare in most other global populations. The aim of the present study was to assess the association of CREBRF variants with obesity and diabetes in Pacific Islander (largely Marianas and Micronesian) populations from Guam and Saipan.

Methods

CREBRF rs12513649 and rs373863828 were genotyped in 2022 participants in a community-based cross-sectional study designed to identify determinants of diabetes and end-stage renal disease (ESRD). Associations were analysed with adjustment for age, sex, ESRD and the first four genetic principal components from a genome-wide association study (to account for population stratification); a genomic control procedure was used to account for residual stratification.

Results

The G allele at rs12513649 had an overall frequency of 7.7%, which varied from 2.2% to 20.7% across different Marianas and Micronesian populations; overall frequency of the A allele at rs373863828 was 4.2% (range: 1.1–5.4%). The G allele at rs12513649 was associated with higher BMI (β=1.55 kg/m2 per copy; p=0.0026) as was the A allele at rs373863828 (β=1.48 kg/m2, p=0.033). The same alleles were associated with lower risk of diabetes (OR per copy: 0.63 [p=0.0063] and 0.49 [p=0.0022], respectively). Meta-analyses combining the current results with previous results in Polynesians showed a strong association between the A allele at rs373863828 and BMI (β=1.38 kg/m2;p=2.5×l0−29) and diabetes (OR=0.65, p=1.5×l0−13).

Conclusions interpretation

These results confirm the associations of CREBRF variants with higher BMI and lower risk of diabetes and, importantly, they suggest that these variants contribute to the risk of obesity and diabetes in Oceanic populations.

Comments

Original published version available at doi.org/10.1007/s00125-019-4932-z

Publication Title

Diabetologia

DOI

10.1007/s00125-019-4932-z

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics

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