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FältnamnIndikatorerMetadata
00010106naa a2200817 4500
001oai:gup.ub.gu.se/295123
003SwePub
008240528s2020 | |||||||||||000 ||eng|
009oai:lup.lub.lu.se:80680d76-df1d-4f30-aeef-bbe43bd73b95
0247 a https://gup.ub.gu.se/publication/2951232 URI
0247 a https://doi.org/10.1371/journal.pmed.10031522 DOI
0247 a https://lup.lub.lu.se/record/80680d76-df1d-4f30-aeef-bbe43bd73b952 URI
040 a (SwePub)gud (SwePub)lu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Forgetta, V.u Lady Davis Institute for Medical Research,Jewish General Hospital,McGill University4 aut
2451 0a Development of a polygenic risk score to improve screening for fracture risk: A genetic risk prediction study
264 c 2020-07-02
264 1b Public Library of Science (PLoS),c 2020
520 a Background Since screening programs identify only a small proportion of the population as eligible for an intervention, genomic prediction of heritable risk factors could decrease the number needing to be screened by removing individuals at low genetic risk. We therefore tested whether a polygenic risk score for heel quantitative ultrasound speed of sound (SOS)-a heritable risk factor for osteoporotic fracture-can identify low-risk individuals who can safely be excluded from a fracture risk screening program. Methods and findings A polygenic risk score for SOS was trained and selected in 2 separate subsets of UK Biobank (comprising 341,449 and 5,335 individuals). The top-performing prediction model was termed "gSOS", and its utility in fracture risk screening was tested in 5 validation cohorts using the National Osteoporosis Guideline Group clinical guidelines (N= 10,522 eligible participants). All individuals were genome-wide genotyped and had measured fracture risk factors. Across the 5 cohorts, the average age ranged from 57 to 75 years, and 54% of studied individuals were women. The main outcomes were the sensitivity and specificity to correctly identify individuals requiring treatment with and without genetic prescreening. The reference standard was a bone mineral density (BMD)-based Fracture Risk Assessment Tool (FRAX) score. The secondary outcomes were the proportions of the screened population requiring clinical-risk-factor-based FRAX (CRF-FRAX) screening and BMD-based FRAX (BMD-FRAX) screening. gSOS was strongly correlated with measured SOS (r(2)= 23.2%, 95% CI 22.7% to 23.7%). Without genetic prescreening, guideline recommendations achieved a sensitivity and specificity for correct treatment assignment of 99.6% and 97.1%, respectively, in the validation cohorts. However, 81% of the population required CRF-FRAX tests, and 37% required BMD-FRAX tests to achieve this accuracy. Using gSOS in prescreening and limiting further assessment to those with a low gSOS resulted in small changes to the sensitivity and specificity (93.4% and 98.5%, respectively), but the proportions of individuals requiring CRF-FRAX tests and BMD-FRAX tests were reduced by 37% and 41%, respectively. Study limitations include a reliance on cohorts of predominantly European ethnicity and use of a proxy of fracture risk. Conclusions Our results suggest that the use of a polygenic risk score in fracture risk screening could decrease the number of individuals requiring screening tests, including BMD measurement, while maintaining a high sensitivity and specificity to identify individuals who should be recommended an intervention. Author summaryWhy was this study done? Osteoporosis screening identifies only a small proportion of the screened population to be eligible for intervention. The prediction of heritable risk factors using polygenic risk scores could decrease the number of screened individuals by reassuring those with low genetic risk. We investigated whether the genetic prediction of heel quantitative ultrasound speed of sound (SOS)-a heritable risk factor for osteoporotic fracture-could be incorporated into an established screening guideline to identify individuals at low risk for osteoporosis. What did the researchers do and find? Using UK Biobank, we developed a polygenic risk score (gSOS) consisting of 21,717 genetic variants that was strongly correlated with SOS ( = 23.2%). Using the National Osteoporosis Guideline Group clinical assessment guidelines in 5 validation cohorts, we estimate that reassuring individuals with a high gSOS, rather than doing further assessments, could reduce the number of clinical-risk-factor-based Fracture Risk Assessment Tool (FRAX) tests and bone-density-measurement-based FRAX tests by 37% and 41%, respectively, while maintaining a high sensitivity and specificity to identify individuals who should be recommended an intervention. What do these findings mean? We show that genetic pre-screening could reduce the number of screening tests needed to identify individuals at risk of osteoporotic fractures. Therefore, the potential exists to improve the efficiency of osteoporosis screening programs without large losses in sensitivity or specificity to identify individuals who should receive an intervention. Further translational studies are needed to test the clinical applications of this polygenic risk score; however, our work shows how such scores could be tested in the clinic.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Ortopedi0 (SwePub)302112 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Orthopaedics0 (SwePub)302112 hsv//eng
653 a bone-mineral density
653 a quantitative ultrasound
653 a osteoporotic fractures
653 a cost-effectiveness
653 a older women
653 a uk biobank
653 a association
653 a strategies
653 a management
653 a diagnosis
653 a General & Internal Medicine
7001 a Keller-Baruch, J.u McGill University4 aut
7001 a Forest, M.u Lady Davis Institute for Medical Research,Jewish General Hospital,McGill University4 aut
7001 a Durand, A.u McGill University4 aut
7001 a Bhatnagar, S.u Lady Davis Institute for Medical Research,Jewish General Hospital,McGill University4 aut
7001 a Kemp, J. P.u University of Bristol,University of Queensland,McGill University4 aut
7001 a Nethander, Maria,d 1980u University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Core Facilities, Bioinformatics,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Core Facilities, Bioinformatics4 aut0 (Swepub:gu)xnetma
7001 a Evans, D.u California Pacific Medical Center,University of Bristol,University of Queensland4 aut
7001 a Morris, J. A.u McGill University,Lady Davis Institute for Medical Research,Jewish General Hospital4 aut
7001 a Kiel, D. P.u Broad Institute,Beth Israel Deaconess Medical Center,Harvard University4 aut
7001 a Rivadeneira, F.u Erasmus University Medical Center4 aut
7001 a Johansson, H.u Australian Catholic University,University of Sheffield4 aut
7001 a Harvey, N. C.u University of Southampton,University Hospital Southampton,University of Oxford4 aut
7001 a Mellström, Dan,d 1945u University of Gothenburg,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 Nutrition4 aut0 (Swepub:gu)xmelda
7001 a Karlsson, Magnusu 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 Hospital4 aut0 (Swepub:lu)orto-mka
7001 a Cooper, C.4 aut
7001 a Evans, D. M.4 aut
7001 a Clarke, R.u University of Oxford4 aut
7001 a Kanis, J. A.u Australian Catholic University,University of Sheffield4 aut
7001 a Orwoll, E.u Oregon Health & Science University4 aut
7001 a McCloskey, E. V.u University of Sheffield,Sheffield Teaching Hospitals4 aut
7001 a Ohlsson, Claes,d 1965u University of Gothenburg,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 Nutrition4 aut0 (Swepub:gu)xohlcl
7001 a Pineau, J.4 aut
7001 a Leslie, W. D.u University of Manitoba4 aut
7001 a Greenwood, C. M. T.u Lady Davis Institute for Medical Research,McGill University,Jewish General Hospital4 aut
7001 a Richards, J. B.u Jewish General Hospital,King's College London,McGill University,Lady Davis Institute for Medical Research4 aut
7102 a Lady Davis Institute for Medical Researchb Jewish General Hospital4 org
7730 t PLoS medicined : Public Library of Science (PLoS)g 17:7q 17:7x 1549-1277x 1549-1676
8564 u https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003152&type=printable
8564 u http://dx.doi.org/10.1371/journal.pmed.1003152x freey FULLTEXT
8564 8u https://gup.ub.gu.se/publication/295123
8564 8u https://doi.org/10.1371/journal.pmed.1003152
8564 8u https://lup.lub.lu.se/record/80680d76-df1d-4f30-aeef-bbe43bd73b95

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