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Genetics and Epigenetics

The Māori and Pacific specific CREBRF variant and adult height

International Journal of Obesity volume 44, pages 748–752 (2020)Cite this article

Subjects

Abstract

Background

The CREBRF missense variant (p.Arg457Gln) is paradoxically associated with lower risk of type 2 diabetes, yet higher body mass index (BMI). Here we sought to determine whether this CREBRF variant might be associated with adult height.

Methods

Linear regression was used to analyse the association of the CREBRF minor (A) allele with height in 2286 Māori and Pacific adults living in Aotearoa/New Zealand. A potential type 2 diabetes index event was corrected to account for a bias that may be the cause of paradoxical association between the CREBRF diabetes-protective allele and higher BMI and height.

Results

The CREBRF protective allele was associated with increased adult height (ß = 1.25 cm, P = 3.9 × 10−6), with the effect being more pronounced in males. The lower odds of diabetes remained similar when analyses were adjusted for height (OR = 0.67–0.65). We found no evidence of a diabetes index event bias to explain the paradoxical effect of CREBRF with either BMI or height and diabetes. The orthologous CREBRF p.Arg457Gln variant was created in knock-in mice to independently assess the effect of the variant, and length was found to be greater in male mice at 8 weeks of age.

Conclusion

These data taken together indicate that CREBRF p.Arg457Gln is associated with taller stature in Māori and Pacific adults.

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Funding

The Health Research Council of New Zealand (grant no 08/075, 10/548, 11/1075, 14/527) and the Maurice Wilkins Centre funded this study. LKM is supported by an Australian Research Training Program Scholarship. HY is funded by Diabetes UK RD Lawrence fellowship (grant 17/0005594). The funders had no role in the study design, interpretation or in the decision to submit these results for publication.

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Author notes

  1. These authors contributed equally: Louise K. Metcalfe, Mohanraj Krishnan

Authors and Affiliations

  1. Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia

    Louise K. Metcalfe, Nigel Turner & Greg Smith

  2. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

    Mohanraj Krishnan, Janak De Zoysa, Nicola Dalbeth & Rinki Murphy

  3. Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, UK

    Hanieh Yaghootkar

  4. Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    Troy L. Merry

  5. Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand

    Troy L. Merry, Ofa Dewes, Tony R. Merriman, Peter Shepherd & Rinki Murphy

  6. Department of Molecular Medicine & Pathology, University of Auckland, Auckland, New Zealand

    Ofa Dewes & Peter Shepherd

  7. Ngāti Porou Hauora Charitable Trust, Te Puia Springs, Tairāwhiti East Coast, New Zealand

    Jennie Harré Hindmarsh

  8. Renal Service, Waitemata District Health Board, Auckland, New Zealand

    Janak De Zoysa

  9. Dept of Medicine, University of Otago, Christchurch, New Zealand

    Lisa K. Stamp

  10. Dept of Biochemistry, University of Otago, Dunedin, New Zealand

    Tony R. Merriman

Authors
  1. Louise K. Metcalfe
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  2. Mohanraj Krishnan
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  3. Nigel Turner
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  4. Hanieh Yaghootkar
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  5. Troy L. Merry
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  6. Ofa Dewes
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  7. Jennie Harré Hindmarsh
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  8. Janak De Zoysa
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  9. Nicola Dalbeth
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  10. Lisa K. Stamp
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  11. Tony R. Merriman
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  12. Greg Smith
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  13. Peter Shepherd
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  14. Rinki Murphy
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Contributions

RM, LKM, MK, HY, TM and PS contributed to the design of the study. OD, ND, LKS, JHH, JDZ, RM contributed to participant data collection. PS, GS, TLM, LKM and NT contributed to animal data collection. RM and MK drafted the paper and all authors reviewed this. The paper was approved by all authors.

Corresponding author

Correspondence to Rinki Murphy.

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The authors declare that they have no conflict of interest.

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Metcalfe, L.K., Krishnan, M., Turner, N. et al. The Māori and Pacific specific CREBRF variant and adult height. Int J Obes 44, 748–752 (2020). https://doi.org/10.1038/s41366-019-0437-6

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