Discordant association of the CREBRF rs373863828 minor allele with increased body mass index and protection from type 2 diabetes in Maori and Pacific (Polynesian) people living in New Zealand

Krishnan, M.; Major, T. J.; Topless, R. K.; Dewes, O.; Yu, L.; Thompson, J. M.; McCowan, L.; de Zoysa, J.; Stamp, L. K.; Dalbeth, N.; Harre Hindmarsh, J.; Rapana, N.; Deka, R.; Eng, W. W.; Weeks, D. E.; Minster, R. L.; McGarvey, S. T.; Viali, S.; Wilcox, P.; Grattan, D.; Shepherd, P. R.; Shelling, A. N.; Murphy, R.; Merriman, T. R.

doi:10.1101/188110

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bioRxiv · 10.1101/188110

Discordant association of the CREBRF rs373863828 minor allele with increased body mass index and protection from type 2 diabetes in Maori and Pacific (Polynesian) people living in New Zealand

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Abstract

Aim/HypothesesThe minor allele of CREBRF rs373863828 associates with increased body mass index (BMI) and reduced risk of type 2 diabetes (T2D) in the Samoan population of Samoa and American Samoa. Our aim was to test rs373863828 for association with BMI and odds of T2D, gout and chronic kidney disease (CKD) in M[a]ori and Pacific (Polynesian) people living in Aotearoa New Zealand in 2,286 adults.\n\nMethodsAssociation analyses were performed by linear and logistic regression with BMI, log-transformed BMI, waist circumference, T2D, gout and CKD. Analyses were adjusted for age, sex, the first four genome-wide principal components, and (when appropriate) BMI, waist circumference and T2D.\n\nResultsFor the minor allele of rs373863828 the effect size for log-transformed BMI was 0.038 (95% CI [0.022-0.055], P=4.8x10-6) and for T2D was OR=0.59 (95% CI [0.47-0.73], P=1.9x10-6). There was no evidence for association of genotype with variance in BMI (P=0.13). Nor was there evidence for association with serum urate ({beta}=0.012 mmol/L, Pc=0.10), gout (OR=1.00, P=0.98) or CKD (OR=0.91, P=0.59).\n\nConclusions/interpretationOur results replicated, with very similar effect sizes, association of the minor allele of rs373863828 with higher BMI but lower odds of T2D among New Zealand Polynesian adults, as in Samoan adults living in Samoa and American Samoa.

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Krishnan, M., Major, T. J., Topless, R. K., Dewes, O., Yu, L., Thompson, J. M., McCowan, L., de Zoysa, J., Stamp, L. K., Dalbeth, N., Harre Hindmarsh, J., Rapana, N., Deka, R., Eng, W. W., Weeks, D. E., Minster, R. L., McGarvey, S. T., Viali, S., Wilcox, P., Grattan, D., Shepherd, P. R., Shelling, A. N., Murphy, R., Merriman, T. R.. 2017-09-13. Discordant association of the CREBRF rs373863828 minor allele with increased body mass index and protection from type 2 diabetes in Maori and Pacific (Polynesian) people living in New Zealand. https://doi.org/10.1101/188110

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