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

作者：Krishnan Mohanraj; Major Tanya J; Topless Ruth K; Dewes Ofa; Yu Lennex; Thompson John M D; McCowan Lesley; de Zoysa Janak; Stamp Lisa K; Dalbeth Nicola; Hindmarsh Jennie Harre; Rapana Nuku; Deka Ranjan; Eng Winston W H; Weeks Daniel E; Minster Ryan L; McGarvey Stephen T; Viali Satupa'itea; Naseri Take; Reupena Muagututi'a Sefuiva; Wilcox Phillip; Grattan David; Shepherd Peter R; Shelling Andrew N; Murphy Rinki; Merriman Tony R^*

来源：Diabetologia, 2018, 61(7): 1603-1613.

DOI：10.1007/s00125-018-4623-1

• Association
• BMI
• CREBRF
• Genetic
• Maori
• Obesity
• Pacific
• Polynesian
• Type 2 diabetes

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 MAori 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 x 10(-6)) for log-transformed BMI, with OR 0.59 (95% CI 0.47, 0.73, p = 1.9 x 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 (beta = 0.012 mmol/l, p(corrected) = 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.

• 出版日期2018-7