Mohanraj Krishnan1,2, Tanya J Major3, Ruth K Topless3, Ofa Dewes4, Lennex Yu5, John M D Thompson1,6, Lesley McCowan1, Janak de Zoysa7, Lisa K Stamp8, Nicola Dalbeth2, Jennie Harré Hindmarsh9, Nuku Rapana10, Ranjan Deka11, Winston W H Eng12, Daniel E Weeks12,13, Ryan L Minster13, Stephen T McGarvey14, Satupa'itea Viali15, Take Naseri16, Muagututi'a Sefuiva Reupena17, Phillip Wilcox18, David Grattan4,19, Peter R Shepherd2,4, Andrew N Shelling1, Rinki Murphy2,4, Tony R Merriman20,21. 1. Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand. 2. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland University of Auckland, Auckland, New Zealand. 3. Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin, 9054, New Zealand. 4. Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand. 5. Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand. 6. Department of Paediatrics, Child and Youth Health, University of Auckland, Auckland, New Zealand. 7. Renal Services, Waitemata District Health Board, Auckland, New Zealand. 8. Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand. 9. Ngāti Porou Hauora Charitable Trust, Te Puia Springs, Tairāwhiti East Coast, New Zealand. 10. Pukapuka Community of New Zealand Inc., Mangere, Auckland, New Zealand. 11. Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 12. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. 13. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. 14. International Health Institute, Department of Epidemiology, Brown University School of Public Health, and Department of Anthropology, Brown University, Providence, RI, USA. 15. Samoa National Health Service, Apia, Samoa. 16. Ministry of Health, Government of Samoa, Apia, Samoa. 17. Bureau of Statistics, Government of Samoa, Apia, Samoa. 18. Department of Mathematics and Statistics, University of Otago, Dunedin, New Zealand. 19. Department of Anatomy, University of Otago, Dunedin, New Zealand. 20. Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin, 9054, New Zealand. tony.merriman@otago.ac.nz. 21. Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand. tony.merriman@otago.ac.nz.
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.
AIMS/HYPOTHESIS: The A (minor) allele of CREBRFrs373863828 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 CREBRFrs373863828 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.
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