The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort
Abstract Genome-wide association studies (GWAS) have identified genetic variants robustly associated with asthma. A potential near-term clinical application is to calculate polygenic risk score (PRS) to improve disease risk prediction. The value of PRS, as part of numerous multi-source variables use...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12890-025-03486-3 |
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| author | Martin Pariès Stéphanie Bougeard Aida Eslami Zhonglin Li Michel Laviolette Louis-Philippe Boulet Evelyne Vigneau Yohan Bossé |
| author_facet | Martin Pariès Stéphanie Bougeard Aida Eslami Zhonglin Li Michel Laviolette Louis-Philippe Boulet Evelyne Vigneau Yohan Bossé |
| author_sort | Martin Pariès |
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| description | Abstract Genome-wide association studies (GWAS) have identified genetic variants robustly associated with asthma. A potential near-term clinical application is to calculate polygenic risk score (PRS) to improve disease risk prediction. The value of PRS, as part of numerous multi-source variables used to define asthma, remains unclear. This study aims to evaluate PRS and define most informative thresholds in relation to conventional clinical and physiological criteria of asthma using a multivariate statistical method. Clinical and genome-wide genotyping data were obtained from the Quebec City Case-Control Asthma Cohort (QCCCAC), which is an independent cohort from previous GWAS. PRS was derived using LDpred2 and integrated with other asthma phenotypes by means of Principal Component Analysis with Optimal Scaling (PCAOS). PRS was considered using ‘ordinal level of scaling’ to account for non-linear information. In two dimensional PCAOS space, the first component delineated individuals with and without asthma, whereas the severity of asthma was discerned on the second component. The positioning of high vs. low PRS in this space matched the presence and absence of airway hyperresponsiveness, showing that PRS delineated cases and controls at the same extent as a positive bronchial challenge test. The top 10% and the bottom 5% of the PRS were the most informative thresholds to define individuals at high and low genetic risk of asthma in this cohort. PRS used in a multivariate method offers a decision-making space similar to hyperresponsiveness in this cohort and highlights the most informative and asymmetrical thresholds to define high and low genetic risk of asthma. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | BMC Pulmonary Medicine |
| spelling | doaj-art-384dc89c9e524334bfea07738a36bc002025-01-19T12:08:22ZengBMCBMC Pulmonary Medicine1471-24662025-01-0125111110.1186/s12890-025-03486-3The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma CohortMartin Pariès0Stéphanie Bougeard1Aida Eslami2Zhonglin Li3Michel Laviolette4Louis-Philippe Boulet5Evelyne Vigneau6Yohan Bossé7Oniris, INRAE, StatSCAnses (French Agency for Food, Environmental and Occupational Health and Safety)Institut universitaire de cardiologie et de pneumologie de Québec – Université LavalInstitut universitaire de cardiologie et de pneumologie de Québec – Université LavalInstitut universitaire de cardiologie et de pneumologie de Québec – Université LavalInstitut universitaire de cardiologie et de pneumologie de Québec – Université LavalOniris, INRAE, StatSCInstitut universitaire de cardiologie et de pneumologie de Québec – Université LavalAbstract Genome-wide association studies (GWAS) have identified genetic variants robustly associated with asthma. A potential near-term clinical application is to calculate polygenic risk score (PRS) to improve disease risk prediction. The value of PRS, as part of numerous multi-source variables used to define asthma, remains unclear. This study aims to evaluate PRS and define most informative thresholds in relation to conventional clinical and physiological criteria of asthma using a multivariate statistical method. Clinical and genome-wide genotyping data were obtained from the Quebec City Case-Control Asthma Cohort (QCCCAC), which is an independent cohort from previous GWAS. PRS was derived using LDpred2 and integrated with other asthma phenotypes by means of Principal Component Analysis with Optimal Scaling (PCAOS). PRS was considered using ‘ordinal level of scaling’ to account for non-linear information. In two dimensional PCAOS space, the first component delineated individuals with and without asthma, whereas the severity of asthma was discerned on the second component. The positioning of high vs. low PRS in this space matched the presence and absence of airway hyperresponsiveness, showing that PRS delineated cases and controls at the same extent as a positive bronchial challenge test. The top 10% and the bottom 5% of the PRS were the most informative thresholds to define individuals at high and low genetic risk of asthma in this cohort. PRS used in a multivariate method offers a decision-making space similar to hyperresponsiveness in this cohort and highlights the most informative and asymmetrical thresholds to define high and low genetic risk of asthma.https://doi.org/10.1186/s12890-025-03486-3AsthmaThresholdPolygenic risk scoreMultivariate methodOptimal scalingCohort study |
| spellingShingle | Martin Pariès Stéphanie Bougeard Aida Eslami Zhonglin Li Michel Laviolette Louis-Philippe Boulet Evelyne Vigneau Yohan Bossé The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort BMC Pulmonary Medicine Asthma Threshold Polygenic risk score Multivariate method Optimal scaling Cohort study |
| title | The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort |
| title_full | The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort |
| title_fullStr | The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort |
| title_full_unstemmed | The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort |
| title_short | The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort |
| title_sort | clinical value and most informative threshold of polygenic risk score in the quebec city case control asthma cohort |
| topic | Asthma Threshold Polygenic risk score Multivariate method Optimal scaling Cohort study |
| url | https://doi.org/10.1186/s12890-025-03486-3 |
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