Genetically Predicted Body Mass Index and Mortality in COPD
RATIONALE: BMI is associated with COPD mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate causal mechanisms and predict risk.
OBJECTIVES: To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD.
METHODS: We developed a polygenic score for BMI (PGSBMI) and tested for associations of the PGSBMI with all-cause, respiratory, and cardiovascular mortality in participants with COPD from the COPDGene, ECLIPSE, and Framingham Heart studies. We calculated the difference between measured BMI and PGS-predicted BMI (BMIdiff) and categorized participants into groups of discordantly low (BMIdiff < 20th percentile), concordant (BMIdiff between 20th - 80th percentile), and discordantly high (BMIdiff > 80th percentile) BMI. We applied Cox models, examined potential non-linear associations of the PGSBMI and BMIdiff with mortality, and summarized results with meta-analysis.
MEASUREMENTS AND MAIN RESULTS: We observed significant non-linear associations of measured BMI and BMIdiff, but not PGSBMI, with all-cause mortality. In meta-analyses, a one standard deviation increase in the PGSBMI was associated with an increased hazard for cardiovascular mortality (HR=1.29, 95% CI=1.12-1.49), but not with respiratory or all-cause mortality. Compared to participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher mortality risk for all-cause (HR=1.57, CI=1.41-1.74) and respiratory death (HR=2.01, CI=1.61-2.51).
CONCLUSIONS: In people with COPD, higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with discordantly low BMI have higher all-cause and respiratory mortality compared to those with concordant BMI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
American journal of respiratory and critical care medicine - (2024) vom: 12. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Jingzhou [VerfasserIn] |
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| Links: |
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| Themen: |
BMI |
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| Anmerkungen: |
Date Revised 14.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1164/rccm.202308-1384OC |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369607414 |
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| 100 | 1 | |a Zhang, Jingzhou |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetically Predicted Body Mass Index and Mortality in COPD |
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| 500 | |a Date Revised 14.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a RATIONALE: BMI is associated with COPD mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate causal mechanisms and predict risk | ||
| 520 | |a OBJECTIVES: To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD | ||
| 520 | |a METHODS: We developed a polygenic score for BMI (PGSBMI) and tested for associations of the PGSBMI with all-cause, respiratory, and cardiovascular mortality in participants with COPD from the COPDGene, ECLIPSE, and Framingham Heart studies. We calculated the difference between measured BMI and PGS-predicted BMI (BMIdiff) and categorized participants into groups of discordantly low (BMIdiff < 20th percentile), concordant (BMIdiff between 20th - 80th percentile), and discordantly high (BMIdiff > 80th percentile) BMI. We applied Cox models, examined potential non-linear associations of the PGSBMI and BMIdiff with mortality, and summarized results with meta-analysis | ||
| 520 | |a MEASUREMENTS AND MAIN RESULTS: We observed significant non-linear associations of measured BMI and BMIdiff, but not PGSBMI, with all-cause mortality. In meta-analyses, a one standard deviation increase in the PGSBMI was associated with an increased hazard for cardiovascular mortality (HR=1.29, 95% CI=1.12-1.49), but not with respiratory or all-cause mortality. Compared to participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher mortality risk for all-cause (HR=1.57, CI=1.41-1.74) and respiratory death (HR=2.01, CI=1.61-2.51) | ||
| 520 | |a CONCLUSIONS: In people with COPD, higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with discordantly low BMI have higher all-cause and respiratory mortality compared to those with concordant BMI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BMI | |
| 650 | 4 | |a COPD | |
| 650 | 4 | |a cardiovascular mortality | |
| 650 | 4 | |a respiratory mortality | |
| 650 | 4 | |a weight loss | |
| 700 | 1 | |a Moll, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Hobbs, Brian D |e verfasserin |4 aut | |
| 700 | 1 | |a Bakke, Per |e verfasserin |4 aut | |
| 700 | 1 | |a Regan, Elizabeth A |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Hanfei |e verfasserin |4 aut | |
| 700 | 1 | |a Dupuis, Josée |e verfasserin |4 aut | |
| 700 | 1 | |a Chiles, Joe W |c 3rd |e verfasserin |4 aut | |
| 700 | 1 | |a McDonald, Merry-Lynn N |e verfasserin |4 aut | |
| 700 | 1 | |a Divo, Miguel J |e verfasserin |4 aut | |
| 700 | 1 | |a Silverman, Edwin K |e verfasserin |4 aut | |
| 700 | 1 | |a Celli, Bartolome R |e verfasserin |4 aut | |
| 700 | 1 | |a O'Connor, George T |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Michael H |e verfasserin |4 aut | |
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