Genetic Prediction of Lifetime Risk of Fracture
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
CONTEXT: Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth.
OBJECTIVE: To examine the association between a polygenic risk score (PRS) and lifetime fracture risk.
METHODS: This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis.
RESULTS: The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS > 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively.
CONCLUSION: A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:108 |
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| Enthalten in: |
The Journal of clinical endocrinology and metabolism - 108(2023), 11 vom: 18. Okt., Seite e1403-e1412 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ho-Le, Thao P [VerfasserIn] |
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| Links: |
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| Themen: |
Fracture |
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| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 24.10.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1210/clinem/dgad254 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM356686043 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a CONTEXT: Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth | ||
| 520 | |a OBJECTIVE: To examine the association between a polygenic risk score (PRS) and lifetime fracture risk | ||
| 520 | |a METHODS: This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis | ||
| 520 | |a RESULTS: The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS > 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively | ||
| 520 | |a CONCLUSION: A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a fracture | |
| 650 | 4 | |a genetic profiling | |
| 650 | 4 | |a genetic variant | |
| 650 | 4 | |a osteoporosis | |
| 650 | 4 | |a residual lifetime risk | |
| 700 | 1 | |a Tran, Thach S |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Huy G |e verfasserin |4 aut | |
| 700 | 1 | |a Center, Jacqueline R |e verfasserin |4 aut | |
| 700 | 1 | |a Eisman, John A |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Tuan V |e verfasserin |4 aut | |
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