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Epidemiology and Population Health

A missense variant in CREBRF, rs373863828, is associated with fat-free mass, not fat mass in Samoan infants

International Journal of Obesity volume 45, pages 45–55 (2021)Cite this article

Subjects

Abstract

Background/objectives:

In Samoa, where 80% of the adult population is living with obesity, understanding the determinants of adiposity and growth during infancy may inform prevention efforts. We examined the association of a missense variant, rs373863828, in the CREBRF gene with body composition in Samoan infants. Adults with one or more copies of the rs373863828 minor allele (A) have higher odds of obesity, based on body-mass index (BMI), but paradoxically decreased odds of diabetes compared to those without the allele. Our study may offer novel insight into the natural history and pathogenesis of this unexpected relationship.

Subjects/methods:

In a prospective study, we measured body composition in early infancy, and at 2- and 4-months of age using anthropometry and dual-energy x-ray absorptiometry (DXA). We genotyped subjects at the CREBRF rs373863828 locus and compared infants with (AA/AG) and without (GG) the variant. In longitudinal analyses, we calculated the absolute change in each outcome from the early infant to the 4-month assessment, adjusting for baseline and other covariates.

Results:

In cross-sectional analyses, there was no significant difference in infant BMI or fat mass by genotype. After adjusting for covariates, infants with the variant had 4.0 ± 1.8 g more bone mass (p = 0.026) and 210.9 ± 79.6 g more lean mass (p = 0.009) at 4-months and accumulated 176.9 ± 73.0 g more lean mass between the early infant and 4-month assessment (p = 0.017).

Conclusions:

The CREBRF rs373863828 minor allele (A) was not associated with increased BMI or adiposity in Samoan infants, but instead with increased lean and bone mass. Our findings suggest that lean (i.e., muscle) and bone mass accretion should be explored as pathways to explain the “protective” effect of the CREBRF variant against diabetes.

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Fig. 1: Study design and participant flow diagram.

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Acknowledgements

This research was funded by grants from MacMillan Center for International Dissertation Research Fellowships at Yale University; the National Institutes of Health grant number [2 R01 HL093093]; and the National Science Foundation grant number [BCS DDRIG 1749911]. We thank the participating mothers and their infants and the midwives and doctors at Samoa National Health Services who contributed to the study. We would also like to thank Elise Claffey and Madison Rodman for their contributions to data collection, Richard Bribiescas for his support with the study design, and Claudia Valeggia for her feedback on drafts of this manuscript.

Author information

Authors and Affiliations

  1. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA

    K. J. Arslanian, A. Pomer & N. L. Hawley

  2. Department of Anthropology, Yale University, New Haven, CT, USA

    K. J. Arslanian & N. L. Hawley

  3. Obstetrics & Gynecology, Tupua Tamasese Meaole Hospital, Samoa National Health Services, Apia, Samoa

    U. T. Fidow

  4. Community Studies Program, University of California-Santa Cruz, Santa Cruz, CA, USA

    T. Atanoa

  5. Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa

    F. Unasa-Apelu

  6. Ministry of Health, Government of Samoa, Apia, Samoa

    T. Naseri

  7. International Health Institute, Brown University School of Public Health, Providence, RI, USA

    A. I. Wetzel & S. T. McGarvey

  8. Deakin University, Institute for Physical Activity and Nutrition, Geelong, VIC, Australia

    R. L. Duckham

  9. Australian Institute for Musculoskeletal Sciences (AIMSS), The University of Melbourne and Western Health, St. Albans, Australia

    R. L. Duckham

  10. Departments of Epidemiology and Anthropology, Brown University, Providence, RI, USA

    S. T. McGarvey

  11. Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    J. A. Strayer & E. E. Kershaw

  12. Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA

    D. E. Weeks

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  1. K. J. Arslanian
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Correspondence to N. L. Hawley.

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Arslanian, K.J., Fidow, U.T., Atanoa, T. et al. A missense variant in CREBRF, rs373863828, is associated with fat-free mass, not fat mass in Samoan infants. Int J Obes 45, 45–55 (2021). https://doi.org/10.1038/s41366-020-00659-4

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