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
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.
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.
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).
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.
KeywordsAssociation BMI CREBRF Genetic Māori Obesity Pacific Polynesian Type 2 diabetes
Akaike’s information criterion
Chronic kidney disease
cAMP-responsive element binding protein 3
cAMP-responsive element binding protein 3 regulatory factor
Minor allele frequency
The authors sincerely thank the participants for generously donating their time and information to this study. The authors would like to thank J. Drake (Department of Rheumatology, Canterbury District Health Board, Christchurch, New Zealand), J. de Kwant, R. Laurence, C. Franklin and M. House (all Department of Medicine, University of Auckland, Auckland, New Zealand), N. Aupouri, R. Akuhata and C. Ford (all of Ngāti Porou Hauora Charitable Trust, Te Puia Springs, New Zealand) and G. Sexton (Counties Manukau District Health Board, Auckland, New Zealand) for recruitment.
MK, TJM, PRS, RM and TRM contributed to the design of the study. OD, LM, JdZ, LKS, ND, JHH, NR, TN, MSR, RD, STM and SV contributed to data collection, and RKT, LY, JMDT, WWHE, DEW, RLM, PW, DG and ANS contributed to data analysis and interpretation. MK, RM and TRM drafted the manuscript and all of the other authors reviewed it. The manuscript was approved by all authors. TRM is the guarantor of this work.
The Health Research Council of New Zealand (grant no. 08/075, 10/548, 11/1075, 14/527) and the Maurice Wilkins Centre funded the New Zealand component of this study, and the National Institutes of Health funded the Samoa and American Samoa components (grant no. R01-HL093093 and R01-HL133040).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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