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Worldwide variation in hip fracture incidence weakly aligns with genetic divergence between populations

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Abstract

Summary

This study investigates the influence of genetic differentiation in determining worldwide heterogeneity in osteoporosis-related hip fracture rates. The results indicate that global variation in fracture incidence exceeds that expected on the basis of random genetic variance.

Introduction

Worldwide, the incidence of osteoporotic hip fractures varies considerably. This variability is believed to relate mainly to non-genetic factors. It is conceivable, however, that genetic susceptibility indeed differs across populations. Here, we present the first quantitative assessment of the effects of genetic differentiation on global variability in hip fracture rates.

Methods

We investigate the observed variance in publically reported age-standardized rates of hip fracture among 28 populations from around the world relative to the expected variance given the phylogenetic relatedness of these populations. The extent to which these variances are similar constitutes a “phylogenetic signal,” which was measured using the K statistic. Population genetic divergence was calculated using a robust array of genome-wide single nucleotide polymorphisms.

Results

While phylogenetic signal is maximized when K > 1, a K value of only 0.103 was detected in the combined-sex fracture rate pattern across the 28 populations, indicating that fracture rates vary more than expected based on phylogenetic relationships. When fracture rates for the sexes were analyzed separately, the degree of phylogenetic signal was also found to be small (females: K = 0.102; males: K = 0.081).

Conclusions

The lack of a strong phylogenetic signal underscores the importance of factors other than stochastic genetic diversity in shaping worldwide heterogeneity in hip fracture incidence.

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Acknowledgments

We thank Joseph Pickrell for help with the TreeMix software and three anonymous referees for constructive comments.

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Author notes

  1. I. J. Wallace

    Present address: Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, 02138, USA

Authors and Affiliations

  1. Department of Anthropology, Stony Brook University, Stony Brook, NY, 11794, USA

    I. J. Wallace, J. B. Smaers & F. E. Grine

  2. Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY, 11794, USA

    L. R. Botigué & B. M. Henn

  3. Graduate Program in Genetics, Stony Brook University, Stony Brook, NY, 11794, USA

    M. Lin & B. M. Henn

  4. Department of Anatomical Sciences, Stony Brook Medicine, Stony Brook, NY, 11794, USA

    F. E. Grine

Authors
  1. I. J. Wallace
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  2. L. R. Botigué
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  3. M. Lin
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  4. J. B. Smaers
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  5. B. M. Henn
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Corresponding author

Correspondence to I. J. Wallace.

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Conflicts of interest

None.

Funding

Financial support was provided by the Leakey Foundation to I.J.W. L.R.B. was supported by a Beatriu de Pinós Programme Fellowship.

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Wallace, I.J., Botigué, L.R., Lin, M. et al. Worldwide variation in hip fracture incidence weakly aligns with genetic divergence between populations. Osteoporos Int 27, 2867–2872 (2016). https://doi.org/10.1007/s00198-016-3591-x

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  • DOI: https://doi.org/10.1007/s00198-016-3591-x

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