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Article: Calibration of polygenic risk scores is required prior to clinical implementation: results of three common cancers in UKB

TitleCalibration of polygenic risk scores is required prior to clinical implementation: results of three common cancers in UKB
Authors
Keywordsclinical decision-making
genetic predisposition to disease
genetic testing
genetics
medical oncology
Issue Date2022
Citation
Journal of Medical Genetics, 2022, v. 59, n. 3, p. 243-247 How to Cite?
AbstractBackground SNP-based polygenic risk scores have recently been adopted in the clinic for risk assessment of some common diseases. Their validity is supported by a consistent trend between their percentile rank and disease risk in populations. However, for clinical use at the individual level, the reliability of score values is necessary considering they are directly used to calculate remaining lifetime risk. Objectives We assessed the reliability of polygenic score values to estimate prostate cancer (PCa), breast cancer (BCa) and colorectal cancer (CRC) risk in three incident cohorts from the UK Biobank (n>500 000). Methods Cancer-specific Genetic Risk Score (GRS), a well-established population-standardised polygenic risk score, was calculated. Results A systematic bias was found between estimated risks (GRS values) and observed risks; β (95% CI) was 0.67 (0.58-0.76), 0.74 (0.65-0.84) and 0.82 (0.75-0.89), respectively, for PCa, BCa and CRC, all significantly lower than 1.00 (perfect calibration), p<0.001. After applying a correction factor derived from a training data set, the β for corrected GRS values in an independent testing data set were 1.09 (1.05-1.13), 1.00 (0.88-1.12) and 1.08 (0.96-1.21), respectively, for PCa, BCa and CRC. Conclusion Assessing the calibration of polygenic risk scores is necessary and feasible to ensure their reliability prior to clinical implementation.
Persistent Identifierhttp://hdl.handle.net/10722/314366
ISSN
2023 Impact Factor: 3.5
2023 SCImago Journal Rankings: 1.690
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWei, Jun-
dc.contributor.authorShi, Zhuqing-
dc.contributor.authorNa, Rong-
dc.contributor.authorResurreccion, W. Kyle-
dc.contributor.authorWang, Chi Hsiung-
dc.contributor.authorDuggan, David-
dc.contributor.authorZheng, S. Lilly-
dc.contributor.authorHulick, Peter J.-
dc.contributor.authorHelfand, Brian T.-
dc.contributor.authorXu, Jianfeng-
dc.date.accessioned2022-07-20T12:03:46Z-
dc.date.available2022-07-20T12:03:46Z-
dc.date.issued2022-
dc.identifier.citationJournal of Medical Genetics, 2022, v. 59, n. 3, p. 243-247-
dc.identifier.issn0022-2593-
dc.identifier.urihttp://hdl.handle.net/10722/314366-
dc.description.abstractBackground SNP-based polygenic risk scores have recently been adopted in the clinic for risk assessment of some common diseases. Their validity is supported by a consistent trend between their percentile rank and disease risk in populations. However, for clinical use at the individual level, the reliability of score values is necessary considering they are directly used to calculate remaining lifetime risk. Objectives We assessed the reliability of polygenic score values to estimate prostate cancer (PCa), breast cancer (BCa) and colorectal cancer (CRC) risk in three incident cohorts from the UK Biobank (n>500 000). Methods Cancer-specific Genetic Risk Score (GRS), a well-established population-standardised polygenic risk score, was calculated. Results A systematic bias was found between estimated risks (GRS values) and observed risks; β (95% CI) was 0.67 (0.58-0.76), 0.74 (0.65-0.84) and 0.82 (0.75-0.89), respectively, for PCa, BCa and CRC, all significantly lower than 1.00 (perfect calibration), p<0.001. After applying a correction factor derived from a training data set, the β for corrected GRS values in an independent testing data set were 1.09 (1.05-1.13), 1.00 (0.88-1.12) and 1.08 (0.96-1.21), respectively, for PCa, BCa and CRC. Conclusion Assessing the calibration of polygenic risk scores is necessary and feasible to ensure their reliability prior to clinical implementation.-
dc.languageeng-
dc.relation.ispartofJournal of Medical Genetics-
dc.subjectclinical decision-making-
dc.subjectgenetic predisposition to disease-
dc.subjectgenetic testing-
dc.subjectgenetics-
dc.subjectmedical oncology-
dc.titleCalibration of polygenic risk scores is required prior to clinical implementation: results of three common cancers in UKB-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1136/jmedgenet-2020-107286-
dc.identifier.pmid33443076-
dc.identifier.scopuseid_2-s2.0-85098651844-
dc.identifier.volume59-
dc.identifier.issue3-
dc.identifier.spage243-
dc.identifier.epage247-
dc.identifier.eissn1468-6244-
dc.identifier.isiWOS:000760935800004-

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