A polygenic risk score and age of diagnosis of COPD
Copyright ©The authors 2022. For reproduction rights and permissions contact permissionsersnet.org..
BACKGROUND: Genetic susceptibility may be associated with earlier onset of chronic obstructive pulmonary disease (COPD). We hypothesised that a polygenic risk score (PRS) for COPD would be associated with earlier age of diagnosis of COPD.
METHODS: In 6647 non-Hispanic White (NHW) and 2464 African American (AA) participants from COPDGene, and 6812 participants from the Framingham Heart Study (FHS), we tested the relationship of the PRS and age of COPD diagnosis. Age at diagnosis was determined by: 1) self-reported age at COPD diagnosis or 2) age at visits when moderate-to-severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 2-4) was observed on spirometry. We used Cox regression to examine the overall and time-dependent effects of the PRS on incident COPD. In the COPDGene study, we also examined the PRS's predictive value for COPD at age <50 years (COPD50) using logistic regression and area under the curve (AUC) analyses, with and without the addition of other risk factors present at early life (e.g. childhood asthma).
RESULTS: In Cox models, the PRS demonstrated age-dependent associations with incident COPD, with larger effects at younger ages in both cohorts. The PRS was associated with COPD50 (OR 1.55 (95% CI 1.41-1.71) for NHW, OR 1.23 (95% CI 1.05-1.43) for AA and OR 2.47 (95% CI 2.12-2.88) for FHS participants). In COPDGene, adding the PRS to known early-life risk factors improved prediction of COPD50 in NHW (AUC 0.69 versus 0.74; p<0.0001) and AA (AUC 0.61 versus 0.64; p=0.04) participants.
CONCLUSIONS: A COPD PRS is associated with earlier age of diagnosis of COPD and retains predictive value when added to known early-life risk factors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
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| Enthalten in: |
The European respiratory journal - 60(2022), 3 vom: 28. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Jingzhou [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 19.09.2022 Date Revised 16.02.2024 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.1183/13993003.01954-2021 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM336480091 |
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| 100 | 1 | |a Zhang, Jingzhou |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A polygenic risk score and age of diagnosis of COPD |
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| 500 | |a published: Electronic-Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright ©The authors 2022. For reproduction rights and permissions contact permissionsersnet.org. | ||
| 520 | |a BACKGROUND: Genetic susceptibility may be associated with earlier onset of chronic obstructive pulmonary disease (COPD). We hypothesised that a polygenic risk score (PRS) for COPD would be associated with earlier age of diagnosis of COPD | ||
| 520 | |a METHODS: In 6647 non-Hispanic White (NHW) and 2464 African American (AA) participants from COPDGene, and 6812 participants from the Framingham Heart Study (FHS), we tested the relationship of the PRS and age of COPD diagnosis. Age at diagnosis was determined by: 1) self-reported age at COPD diagnosis or 2) age at visits when moderate-to-severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 2-4) was observed on spirometry. We used Cox regression to examine the overall and time-dependent effects of the PRS on incident COPD. In the COPDGene study, we also examined the PRS's predictive value for COPD at age <50 years (COPD50) using logistic regression and area under the curve (AUC) analyses, with and without the addition of other risk factors present at early life (e.g. childhood asthma) | ||
| 520 | |a RESULTS: In Cox models, the PRS demonstrated age-dependent associations with incident COPD, with larger effects at younger ages in both cohorts. The PRS was associated with COPD50 (OR 1.55 (95% CI 1.41-1.71) for NHW, OR 1.23 (95% CI 1.05-1.43) for AA and OR 2.47 (95% CI 2.12-2.88) for FHS participants). In COPDGene, adding the PRS to known early-life risk factors improved prediction of COPD50 in NHW (AUC 0.69 versus 0.74; p<0.0001) and AA (AUC 0.61 versus 0.64; p=0.04) participants | ||
| 520 | |a CONCLUSIONS: A COPD PRS is associated with earlier age of diagnosis of COPD and retains predictive value when added to known early-life risk factors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Xu, Hanfei |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Dandi |e verfasserin |4 aut | |
| 700 | 1 | |a DeMeo, Dawn L |e verfasserin |4 aut | |
| 700 | 1 | |a Silverman, Edwin K |e verfasserin |4 aut | |
| 700 | 1 | |a O'Connor, George T |e verfasserin |4 aut | |
| 700 | 1 | |a Hobbs, Brian D |e verfasserin |4 aut | |
| 700 | 1 | |a Dupuis, Josée |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Michael H |e verfasserin |4 aut | |
| 700 | 1 | |a Moll, Matthew |e verfasserin |4 aut | |
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