| Autor: |
Zhang J; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.; Channing Division of Network Medicine, and., Moll M; Channing Division of Network Medicine, and.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Division of Pulmonary, Critical Care, Sleep, and Allergy, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts., Hobbs BD; Channing Division of Network Medicine, and.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Bakke P; Department of Clinical Science, University of Bergen, Bergen, Norway., Regan EA; Department of Medicine, National Jewish Health, Denver, Colorado., Xu H; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts., Dupuis J; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada., Chiles JW; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and., McDonald MN; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and.; Department of Genetics, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; and., Divo MJ; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Silverman EK; Channing Division of Network Medicine, and.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Celli BR; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., O'Connor GT; The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.; NHLBI Framingham Heart Study, Framingham, Massachusetts., Cho MH; Channing Division of Network Medicine, and.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. |
| Abstrakt: |
Rationale: Body mass index (BMI) is associated with chronic obstructive pulmonary disease (COPD) mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate the 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 (PGS) for BMI (PGS BMI ) and tested for associations of the PGS BMI with all-cause, respiratory, and cardiovascular mortality in participants with COPD from the COPDGene (Genetic Epidemiology of COPD), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), and Framingham Heart studies. We calculated the difference between measured BMI and PGS-predicted BMI (BMI diff ) and categorized participants into groups of discordantly low (BMI diff <20th percentile), concordant (BMI diff between the 20th and 80th percentiles), and discordantly high (BMI diff >80th percentile) BMI. We applied Cox models, examined potential nonlinear associations of the PGS BMI and BMI diff with mortality, and summarized results with meta-analysis. Measurements and Main Results: We observed significant nonlinear associations of measured BMI and BMI diff , but not PGS BMI , with all-cause mortality. In meta-analyses, a one-standard deviation increase in the PGS BMI was associated with an increased hazard for cardiovascular mortality (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.12-1.49), but not for respiratory or all-cause mortality. Compared with participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher risks for all-cause mortality (HR, 1.57; 95% CI, 1.41-1.74) and respiratory death (HR, 2.01; 95% CI, 1.61-2.51). Conclusions: In people with COPD, a higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with a discordantly low BMI have higher all-cause and respiratory mortality rates than those with a concordant BMI. |
