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Improved prediction...
Improved prediction of fracture risk leveraging a genome-wide polygenic risk score
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- Lu, T. Y. (författare)
- Lady Davis Institute for Medical Research,McGill University
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- Forgetta, V. (författare)
- Lady Davis Institute for Medical Research
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- Keller-Baruch, J. (författare)
- Lady Davis Institute for Medical Research
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visa fler...
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- Nethander, Maria, 1980 (författare)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Core Facilities, Bioinformatics,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Core Facilities, Bioinformatics,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska Academy
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- Bennett, D. (författare)
- Oxford University Hospitals NHS Foundation Trust,University of Oxford
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- Forest, M. (författare)
- Lady Davis Institute for Medical Research
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- Bhatnagar, S. (författare)
- McGill University
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- Walters, R. G. (författare)
- University of Oxford
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- Lin, K. (författare)
- University of Oxford
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- Chen, Z. M. (författare)
- University of Oxford
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- Li, L. M. (författare)
- Peking University
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- Karlsson, Magnus (författare)
- Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skåne University Hospital
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- Mellström, Dan, 1945 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska Academy
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- Orwoll, E. (författare)
- Oregon Health & Science University
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- McCloskey, E. V. (författare)
- University of Sheffield
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- Kanis, J. A. (författare)
- Australian Catholic University,University of Sheffield
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- Leslie, W. D. (författare)
- University of Manitoba
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- Clarke, R. J. (författare)
- University of Oxford
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- Ohlsson, Claes, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska University Hospital,Sahlgrenska Academy
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- Greenwood, C. M. T. (författare)
- McGill University,Lady Davis Institute for Medical Research
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- Richards, J. B. (författare)
- Lady Davis Institute for Medical Research,McGill University,King's College London
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(creator_code:org_t)
- 2021-02-03
- 2021
- Engelska.
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 13:1
- Relaterad länk:
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https://genomemedici...
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http://dx.doi.org/10... (free)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Background Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction. Methods We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors. Results A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13-1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727-0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791-0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072. Conclusions We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Ortopedi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Orthopaedics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Genetics & Heredity
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Lu, T. Y.
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Forgetta, V.
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Keller-Baruch, J ...
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Nethander, Maria ...
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Bennett, D.
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Forest, M.
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visa fler...
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Bhatnagar, S.
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Walters, R. G.
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Lin, K.
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Chen, Z. M.
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Li, L. M.
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Karlsson, Magnus
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Mellström, Dan, ...
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Orwoll, E.
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McCloskey, E. V.
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Kanis, J. A.
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Leslie, W. D.
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Clarke, R. J.
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Ohlsson, Claes, ...
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Greenwood, C. M. ...
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Richards, J. B.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Ortopedi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Genome Medicine
- Av lärosätet
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Göteborgs universitet
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Lunds universitet