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A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women

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Abstract

Summary

This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies.

Introduction

Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes—plate-like and rod-like—and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies.

Methods

A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses.

Results

The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (≥1.336) and rod-like as a TPR ratio value in the lowest quartile (≤0.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3–90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7–568.0) to be Chinese-American.

Conclusion

Using extreme phenotype selection, we defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait. The former phenotype is more common in Chinese-American women, while the latter is more typical of Caucasian women. The robustness of these phenotypic associations after controlling for differences in constitution and lifestyle suggest that the TPR ratio may have a genetic basis and that the extreme phenotypes defined in this analysis can be utilized for future studies.

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Acknowledgments

This work was supported by NIH grants K23 AR053507 as well as AR051376, a National Osteoporosis Foundation grant, and the Mary and David Hoar Fellowship Program of the New York Community Trust and the New York Academy of Medicine. We thank Dr. Clyde Wu for his vision and support of this study.

Conflicts of interest

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA

    M. D. Walker, X. S. Liu, C. Zhang, D. J. McMahon & J. P. Bilezikian

  2. Center for Genome Technology and Biomolecular Engineering, Department of Chemical Engineering and Applied Science, Columbia University, New York, NY, 10027, USA

    S. Shi & J. J. Russo

  3. McKay Orthopedic Research Laboratory, Department of Orthopedic Surgery, University of Pennsylvania, Philadelphia, PA, 19104, USA

    X. S. Liu

  4. Bone Bioengineering Laboratory, Department of Biomedical Engineering, Fu Foundation School of Engineering and Applied Science, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY, 10027, USA

    B. Zhou & X. E. Guo

  5. Department of Medicine, Weill Cornell Medical College, New York Presbyterian Lower Manhattan Hospital, New York, NY, 10038, USA

    G. Liu

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  1. M. D. Walker
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  2. S. Shi
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  7. G. Liu
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Correspondence to M. D. Walker.

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Walker, M.D., Shi, S., Russo, J.J. et al. A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women. Osteoporos Int 25, 2787–2795 (2014). https://doi.org/10.1007/s00198-014-2816-0

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