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

Heying Zhou, Seijiro Mori, Tatsuro Ishizaki, Masashi Tanaka, Kumpei Tanisawa, Makiko Naka Mieno, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Yoshiji Yamada, Hideki Ito

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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.

Original languageEnglish
Pages (from-to)685-691
Number of pages7
JournalJournal of Bone and Mineral Metabolism
Volume34
Issue number6
DOIs
Publication statusPublished - 2016 Nov 1

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Femoral Fractures
Autopsy
Confidence Intervals
Single Nucleotide Polymorphism
Iduronidase
Logistic Models
Alleles
Odds Ratio
Werner Syndrome
Homeobox Genes
ROC Curve
Genes
Osteoporosis
Regression Analysis

Keywords

  • Femoral fracture
  • Genetic risk score
  • Osteoporosis
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males. / Zhou, Heying; Mori, Seijiro; Ishizaki, Tatsuro; Tanaka, Masashi; Tanisawa, Kumpei; Mieno, Makiko Naka; Sawabe, Motoji; Arai, Tomio; Muramatsu, Masaaki; Yamada, Yoshiji; Ito, Hideki.

In: Journal of Bone and Mineral Metabolism, Vol. 34, No. 6, 01.11.2016, p. 685-691.

Research output: Contribution to journalArticle

Zhou, H, Mori, S, Ishizaki, T, Tanaka, M, Tanisawa, K, Mieno, MN, Sawabe, M, Arai, T, Muramatsu, M, Yamada, Y & Ito, H 2016, 'Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males', Journal of Bone and Mineral Metabolism, vol. 34, no. 6, pp. 685-691. https://doi.org/10.1007/s00774-015-0718-7
Zhou, Heying ; Mori, Seijiro ; Ishizaki, Tatsuro ; Tanaka, Masashi ; Tanisawa, Kumpei ; Mieno, Makiko Naka ; Sawabe, Motoji ; Arai, Tomio ; Muramatsu, Masaaki ; Yamada, Yoshiji ; Ito, Hideki. / Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males. In: Journal of Bone and Mineral Metabolism. 2016 ; Vol. 34, No. 6. pp. 685-691.
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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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AU - Tanisawa, Kumpei

AU - Mieno, Makiko Naka

AU - Sawabe, Motoji

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