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• W3044000917 abstract "Abstract Introduction Family history is a risk factor for chronic obstructive pulmonary disease (COPD). We previously developed a COPD risk score from genome-wide genetic markers (polygenic risk score, or PRS). Whether the PRS and family history provide complementary or redundant information for predicting COPD and related outcomes is unknown. Methods We assessed the predictive capacity of family history and PRS on COPD and COPD-related outcomes in European ancestry subjects from the COPDGene and ECLIPSE studies. We also performed interaction and mediation analyses. Results In COPDGene, family history and PRS were significantly associated with COPD in a single model (P FamHx = 1.6e-12; P PRS = 5.0e-92). Similar trends were seen in ECLIPSE. Area-under-the-receiver-operator-characteristic-curves (AUCs) for family history, PRS, and the combined predictors for COPD were 0.752, 0.798, and 0.803, respectively. The AUC for a model containing both family history and the PRS was significantly higher than models with PRS (p = 0.00035) or family history (p = 6.1e-29) alone. Both family history and PRS were significantly associated with BODE, SGRQ, and multiple measures of quantitative emphysema and airway thickness. There was a weakly positive interaction between family history and the PRS under the additive, but not the multiplicative scale (RERI = 0.48, p=0.04). Mediation analysis found 16.5% of the effect of family history on risk for COPD was mediated through the PRS [95% CI: 9.4%-24.3%]. Conclusion Family history and the PRS provide complementary information for predicting COPD and related outcomes. Future studies can address the impact of obtaining both measures in clinical practice." @default.
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• W3044000917 date "2020-07-24" @default.
• W3044000917 modified "2023-09-26" @default.
• W3044000917 title "Relative Contributions of Family History and a Polygenic Risk Score on COPD and Related Outcomes: COPDGene and ECLIPSE studies" @default.
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• W3044000917 doi "https://doi.org/10.1101/2020.07.23.20160739" @default.
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