1. 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.
- Author
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Krishnan M, Major TJ, Topless RK, Dewes O, Yu L, Thompson JMD, McCowan L, de Zoysa J, Stamp LK, Dalbeth N, Harré Hindmarsh J, Rapana N, Deka R, Eng WWH, Weeks DE, Minster RL, McGarvey ST, Viali S, Naseri T, Sefuiva Reupena M, Wilcox P, Grattan D, Shepherd PR, Shelling AN, Murphy R, and Merriman TR
- Subjects
- Adult, Aged, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 ethnology, Diabetes Mellitus, Type 2 genetics, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, New Zealand epidemiology, Obesity diagnosis, Obesity ethnology, Phenotype, Polynesia ethnology, Protective Factors, Risk Factors, Body Mass Index, Diabetes Mellitus, Type 2 prevention & control, Native Hawaiian or Other Pacific Islander genetics, Obesity genetics, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins genetics
- 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.- Published
- 2018
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