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  • Brief Communication
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Genetics and Epigenetics

The Māori and Pacific specific CREBRF variant and adult height

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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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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  • DOI: https://doi.org/10.1038/s41366-019-0437-6

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