Association of CREBRF variants with obesity and diabetes in Pacific Islanders from Guam and Saipan
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.
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.
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 × 10−29) and diabetes (OR 0.65, p = 1.5 × 10−13).
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.
KeywordsCREBRF Genetics Marianas Micronesians Obesity Type 2 diabetes mellitus
End-stage renal disease
Genome-wide association study
The authors thank the participants who volunteered for these studies and the staff who helped to conduct them. Particular thanks are due to J. Loebel and V. Ossowski, Phoenix Epidemiology and Clinical Research Branch, for help with laboratory work. This work was presented in part at the 78th Scientific Sessions of the American Diabetes Association, Orlando, FL, USA, 22–26 June 2018.
RLH contributed to study conception and design, data acquisition, analysis and interpretation of data, and drafting the manuscript. SS and RGN contributed to study conception and design, data acquisition, analysis and interpretation of data, and revising the draft for intellectual content. JMC and W-CH contributed to data acquisition, analysis and interpretation of data and revising the draft for intellectual content. WCK contributed to study conception and design, interpretation of data and revising the draft for intellectual content. LIJ, TFA, JDS, SK, NBB, JEC, DM and LJB contributed to data acquisition, interpretation of data, and revising the draft for intellectual content. All authors read and approved the final manuscript. RLH is the guarantor of the integrity of the work.
This work was supported by the intramural research programme of the National Institute of Diabetes and Digestive and Kidney Diseases. The genotyping was conducted in part in facilities constructed under the support of NIH grant C06 RR020547.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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