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Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean\/PRS CI and the population level threshold.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (&gt;\u200990th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12\u20133.50, <jats:italic>P<\/jats:italic>-value = 4.13 \u00d7 10<jats:sup>\u221215<\/jats:sup>) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99\u20132.49, <jats:italic>P<\/jats:italic>-value = 5.70 \u00d7 10<jats:sup>\u221246<\/jats:sup>). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72\u20130.74).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13073-024-01298-4","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T11:05:08Z","timestamp":1707131108000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Impact of individual level uncertainty of lung cancer polygenic 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