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Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males

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Abstract

A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Five SNPs (α-ʟ-iduronidase rs3755955, C7orf58 rs190543052, homeobox C4 rs75256744, G patch domain-containing gene 1 rs2287679, and Werner syndrome rs2230009) showed a significant association (P < 0.05) with the prevalence of femoral fracture in 924 male subjects. Both the unweighted and weighted GRS adequately predicted fracture prevalence; areas under receiver-operating characteristic curves were 0.750 [95 % confidence interval (CI) 0.660–0.840] and 0.770 (95 % CI 0.681–0.859), respectively. Multiple logistic regression analysis revealed that the odds ratio (OR) for the association between fracture prevalence and unweighted GRS ≥3 (n = 124) was 8.39 (95 % CI 4.22–16.69, P < 0.001) relative to a score <3 (n = 797). Likewise, the OR for a weighted GRS of 6–15 (n = 135) was 7.73 (95 % CI 3.89–15.36, P < 0.001) relative to scores of 0–5 (n = 786). The GRS based on risk allele profiles of the five SNPs could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture.

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Acknowledgments

This work was supported by a grant from the Leading Project for Personalized Medicine of the Ministry of Education, Culture, Sports, Science and Technology of Japan (no. 09042037 to S.M.); Grants-in-Aid for Scientific Research (nos. 22240072, 21390459, and 21590411 to M.T. and 18209023, 18018021, 19659149, and 24590746 to Y.Y.); a Grant-in-Aid for the Global COE (Sport Sciences for the Promotion of Active Life to Waseda University) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to M.T.); Grants-in-Aid for Research on Intractable Diseases (Mitochondrial Disease) from the Ministry of Health, Labour and Welfare of Japan (H23-016, H23-119, and H24-005 to M.T.); grants for scientific research from Mitsui Sumitomo Insurance Welfare Foundation (to S.M.); the Pfizer Academic Contribution Fund (to S.M.); Takeda Science Foundation (to M.T.); the Smoking Research Foundation (to T.A. and M.S.); and the Mie Medical Valley Project (to Y.Y.).

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Authors and Affiliations

  1. Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, Itabashi, Tokyo, 173-0015, Japan

    Heying Zhou & Seijiro Mori

  2. Research Team for Human Care, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Tatsuro Ishizaki

  3. Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Masashi Tanaka & Kumpei Tanisawa

  4. Graduate School of Sport Sciences, Waseda University, Saitama, Japan

    Kumpei Tanisawa

  5. Department of Medical Informatics, Center for Information, Jichi Medical University, Tochigi, Japan

    Makiko Naka Mieno

  6. Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Motoji Sawabe

  7. Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

    Tomio Arai

  8. Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Masaaki Muramatsu

  9. Department of Human Functional Genomics, Life Science Research Center, Mie University, Mie, Japan

    Yoshiji Yamada

  10. Local Independent Administrative Agency, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan

    Hideki Ito

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  1. Heying Zhou
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  11. Hideki Ito
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Correspondence to Seijiro Mori.

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Conflicts of interest

Heying Zhou, Seijiro Mori, Tatsuro Ishizaki, Masashi Tanaka, Kumpei Tanisawa, Makiko Naka Mieno, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Yoshiji Yamada, and Hideki Ito declare that they have no conflicts of interest.

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Zhou, H., Mori, S., Ishizaki, T. et al. Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males. J Bone Miner Metab 34, 685–691 (2016). https://doi.org/10.1007/s00774-015-0718-7

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  • DOI: https://doi.org/10.1007/s00774-015-0718-7

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