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dc.contributor.authorRostami, Sina
dc.contributor.authorHoff, Mari
dc.contributor.authorBrown, Matthew A.
dc.contributor.authorHveem, Kristian
dc.contributor.authorVidem, Vibeke
dc.date.accessioned2021-01-05T12:55:19Z
dc.date.available2021-01-05T12:55:19Z
dc.date.created2020-07-22T11:28:35Z
dc.date.issued2020
dc.identifier.citationRheumatology. 2020, 59 (7), .en_US
dc.identifier.issn1462-0324
dc.identifier.urihttps://hdl.handle.net/11250/2721495
dc.description.abstractObjectives: To evaluate selection methods among published single-nucleotide polymorphisms (SNPs) associated with RA to construct predictive genetic risk scores (GRSs) in a population-based setting. Methods: The Nord-Trøndelag Health (HUNT) Study is a prospective cohort study among the whole adult population of northern Trøndelag, Norway. Participants in HUNT2 (1995–1997) and HUNT3 (2006–2008) were included (489 RA cases, 61 584 controls). The initial SNP selection from relevant genome-wide studies included 269 SNPs from 30 studies. Following different selection criteria, SNPs were weighted by published odds ratios. The sum of each person’s carriage of all weighted susceptibility variants was calculated for each GRS. Results: The best-fitting risk score included 27 SNPs [weighted genetic risk score 27 (wGRS27)] and was identified using P-value selection criterion ≤5 × 10−8, the largest possible SNP selection without high linkage disequilibrium (r2 < 0.8), and lasso regression to select for positive coefficients. In a logistic regression model adjusted for gender, age and ever smoking, wGRS27 was associated with RA [odds ratio 1.86 (95% CI 1.71, 2.04) for each S.D. increase, P < 0.001]. The AUC was 0.76 (95% CI 0.74, 0.78). The positive and negative predictive values were 1.6% and 99.7%, respectively, and the positive predictive value was not improved in sensitivity analyses subselecting participants to illustrate settings with increased RA prevalences. Other schemes selected more SNPs but resulted in GRSs with lower predictive ability. Conclusion: Constructing a wGRS based on a smaller selection of informative SNPs improved predictive ability. Even with a relatively high AUC, the low PPV illustrates that there was a large overlap in risk variants among RA patients and controls, precluding clinical usefulness.en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.subjectEpidemiologien_US
dc.subjectEpidemiologyen_US
dc.subjectLeddgikten_US
dc.subjectRheumatoid arthritisen_US
dc.subjectGenetikken_US
dc.subjectGeneticsen_US
dc.titleComparison of methods to construct a genetic risk score for prediction of rheumatoid arthritis in the population-based Nord-Trøndelag Health Study, Norwayen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionacceptedVersionen_US
dc.subject.nsiVDP::Reumatologi: 759en_US
dc.subject.nsiVDP::Rheumatology: 759en_US
dc.source.pagenumber8en_US
dc.source.volume59en_US
dc.source.journalRheumatologyen_US
dc.source.issue7en_US
dc.identifier.doi10.1093/rheumatology/kez638
dc.identifier.cristin1820171
dc.relation.projectNorges forskningsråd: 248817en_US
dc.relation.projectStiftelsen Kristian Gerhard Jebsen: SKGJ-MED-015en_US
dc.description.localcodeLocked until 13.01.2021 due to copyright restrictions. This is a pre-copyedited, author-produced version of an article accepted for publication following peer review. The version of record is available online at: DOI:10.1093/rheumatology/kez638en_US
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode1


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