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Published in: Diabetologia 7/2018

01-07-2018 | Article

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

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

Published in: Diabetologia | Issue 7/2018

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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.
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Literature
1.
2.
go back to reference Loos RJ (2016) CREBRF variant increases obesity risk and protects against diabetes in Samoans. Nat Genet 48:976–978CrossRefPubMed Loos RJ (2016) CREBRF variant increases obesity risk and protects against diabetes in Samoans. Nat Genet 48:976–978CrossRefPubMed
3.
go back to reference Naka I, Furusawa T, Kimura R et al (2017) A missense variant, rs373863828-A (p.Arg457Gln), of CREBRF and body mass index in Oceanic populations. J Hum Genet 62:847–849CrossRefPubMed Naka I, Furusawa T, Kimura R et al (2017) A missense variant, rs373863828-A (p.Arg457Gln), of CREBRF and body mass index in Oceanic populations. J Hum Genet 62:847–849CrossRefPubMed
5.
go back to reference Kilpelainen TO, Zillikens MC, Stancakova A et al (2011) Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 43:753–760CrossRefPubMedPubMedCentral Kilpelainen TO, Zillikens MC, Stancakova A et al (2011) Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 43:753–760CrossRefPubMedPubMedCentral
6.
go back to reference Yaghootkar H, Scott RA, White CC et al (2014) Genetic evidence for a normal-weight “metabolically obese” phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes 63:4369–4377CrossRefPubMedPubMedCentral Yaghootkar H, Scott RA, White CC et al (2014) Genetic evidence for a normal-weight “metabolically obese” phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes 63:4369–4377CrossRefPubMedPubMedCentral
7.
go back to reference Scott RA, Fall T, Pasko D et al (2014) Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Diabetes 63:4378–4387CrossRefPubMedPubMedCentral Scott RA, Fall T, Pasko D et al (2014) Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Diabetes 63:4378–4387CrossRefPubMedPubMedCentral
8.
go back to reference Yaghootkar H, Lotta LA, Tyrrell J et al (2016) Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension, and heart disease. Diabetes 65:2448–2460CrossRefPubMedPubMedCentral Yaghootkar H, Lotta LA, Tyrrell J et al (2016) Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension, and heart disease. Diabetes 65:2448–2460CrossRefPubMedPubMedCentral
9.
go back to reference Virtue S, Vidal-Puig A (2010) Adipose tissue expandability, lipotoxicity and the metabolic syndrome—an allostatic perspective. Biochim Biophys Acta 1801:338–349CrossRefPubMed Virtue S, Vidal-Puig A (2010) Adipose tissue expandability, lipotoxicity and the metabolic syndrome—an allostatic perspective. Biochim Biophys Acta 1801:338–349CrossRefPubMed
10.
go back to reference Winnard D, Wright C, Jackson G et al (2012) Gout, diabetes and cardiovascular disease in the Aotearoa New Zealand adult population: co-prevalence and implications for clinical practice. N Z Med J 126:53–64PubMed Winnard D, Wright C, Jackson G et al (2012) Gout, diabetes and cardiovascular disease in the Aotearoa New Zealand adult population: co-prevalence and implications for clinical practice. N Z Med J 126:53–64PubMed
11.
go back to reference Winnard D, Wright C, Taylor WJ et al (2012) National prevalence of gout derived from administrative health data in Aotearoa New Zealand. Rheumatology (Oxford) 51:901–909CrossRef Winnard D, Wright C, Taylor WJ et al (2012) National prevalence of gout derived from administrative health data in Aotearoa New Zealand. Rheumatology (Oxford) 51:901–909CrossRef
12.
go back to reference Hollis-Moffatt JE, Phipps-Green AJ, Chapman B et al (2012) The renal urate transporter SLC17A1 locus: confirmation of association with gout. Arthritis Res Ther 14:R92CrossRefPubMedPubMedCentral Hollis-Moffatt JE, Phipps-Green AJ, Chapman B et al (2012) The renal urate transporter SLC17A1 locus: confirmation of association with gout. Arthritis Res Ther 14:R92CrossRefPubMedPubMedCentral
13.
go back to reference Robinson PC, Choi HK, Do R, Merriman TR (2016) Insight into rheumatological cause and effect through the use of Mendelian randomization. Nat Rev Rheumatol 12:486–496CrossRefPubMed Robinson PC, Choi HK, Do R, Merriman TR (2016) Insight into rheumatological cause and effect through the use of Mendelian randomization. Nat Rev Rheumatol 12:486–496CrossRefPubMed
16.
go back to reference Terrell JE (2010) Social network analysis of the genetic structure of Pacific islanders. Ann Hum Genet 74:211–232CrossRefPubMed Terrell JE (2010) Social network analysis of the genetic structure of Pacific islanders. Ann Hum Genet 74:211–232CrossRefPubMed
18.
go back to reference Phipps-Green AJ, Merriman ME, Topless R et al (2016) Twenty-eight loci that influence serum urate levels: analysis of association with gout. Ann Rheum Dis 75:124–130CrossRefPubMed Phipps-Green AJ, Merriman ME, Topless R et al (2016) Twenty-eight loci that influence serum urate levels: analysis of association with gout. Ann Rheum Dis 75:124–130CrossRefPubMed
20.
go back to reference Swinburn BA, Ley SJ, Carmichael HE, Plank LD (1999) Body size and composition in Polynesians. Int J Obes Relat Metab Disord 23:1178–1183CrossRefPubMed Swinburn BA, Ley SJ, Carmichael HE, Plank LD (1999) Body size and composition in Polynesians. Int J Obes Relat Metab Disord 23:1178–1183CrossRefPubMed
23.
go back to reference Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–909CrossRefPubMed Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–909CrossRefPubMed
24.
go back to reference Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81:559–575CrossRefPubMedPubMedCentral Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81:559–575CrossRefPubMedPubMedCentral
25.
go back to reference Aulchenko YS, Ripke S, Isaacs A, van Dujin CM (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23:1294–1296CrossRefPubMed Aulchenko YS, Ripke S, Isaacs A, van Dujin CM (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23:1294–1296CrossRefPubMed
27.
go back to reference Akaike H (1974) A new look at the statistical model identification. IEEE Trans Autom Control 19:716–723CrossRef Akaike H (1974) A new look at the statistical model identification. IEEE Trans Autom Control 19:716–723CrossRef
28.
go back to reference Topless RK, Flynn TJ, Cadzow M et al (2015) Association of SLC2A9 genotype with phenotypic variability of serum urate in pre-menopausal women. Front Genet 6:313CrossRefPubMedPubMedCentral Topless RK, Flynn TJ, Cadzow M et al (2015) Association of SLC2A9 genotype with phenotypic variability of serum urate in pre-menopausal women. Front Genet 6:313CrossRefPubMedPubMedCentral
29.
go back to reference Ying Z, Misra V, Verge VM (2014) Sensing nerve injury at the axonal ER: activated Luman/CREB3 serves as a novel axonally synthesized retrograde regeneration signal. Proc Natl Acad Sci U S A 111:16142–16147CrossRefPubMedPubMedCentral Ying Z, Misra V, Verge VM (2014) Sensing nerve injury at the axonal ER: activated Luman/CREB3 serves as a novel axonally synthesized retrograde regeneration signal. Proc Natl Acad Sci U S A 111:16142–16147CrossRefPubMedPubMedCentral
30.
go back to reference Liang G, Audas TE, Li Y et al (2006) Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element. Mol Cell Biol 26:7999–8010CrossRefPubMedPubMedCentral Liang G, Audas TE, Li Y et al (2006) Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element. Mol Cell Biol 26:7999–8010CrossRefPubMedPubMedCentral
32.
go back to reference Kampstra P (2008) Beanplot: a boxplot alternative for visual comparison of distributors. J Stat Softw 28:1–9CrossRef Kampstra P (2008) Beanplot: a boxplot alternative for visual comparison of distributors. J Stat Softw 28:1–9CrossRef
Metadata
Title
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
Authors
Mohanraj Krishnan
Tanya J. Major
Ruth K. Topless
Ofa Dewes
Lennex Yu
John M. D. Thompson
Lesley McCowan
Janak de Zoysa
Lisa K. Stamp
Nicola Dalbeth
Jennie Harré Hindmarsh
Nuku Rapana
Ranjan Deka
Winston W. H. Eng
Daniel E. Weeks
Ryan L. Minster
Stephen T. McGarvey
Satupa’itea Viali
Take Naseri
Muagututi’a Sefuiva Reupena
Phillip Wilcox
David Grattan
Peter R. Shepherd
Andrew N. Shelling
Rinki Murphy
Tony R. Merriman
Publication date
01-07-2018
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 7/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4623-1

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