Exome Sequencing Analysis in Severe, Early-Onset Chronic Obstructive Pulmonary Disease

Qiao, Dandi; Lange, Christoph; Beaty, Terri H.; Crapo, James D.; Barnes, Kathleen C.; Bamshad, Michael J.; Hersh, Craig P.; Morrow, Jarrett; Pinto-Plata, Víctor; Marchetti, Nathaniel; Bueno, Raphael; Celli, Bartolomé R.; Criner, G.J.; Silverman, Edwin K.; Cho, Michael H.

doi:10.1164/rccm.201506-1223oc

Cited by 45 publications

(48 citation statements)

References 48 publications

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“…The authors the explored if candidate variants identified were associated with COPD within the COPDGene cohort (57). Although novel because it targeted COPD using whole-exome sequencing, this study found only trends of association which were non-significant.…”

Section: Genetic Predispositionmentioning

confidence: 99%

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Update in Chronic Obstructive Pulmonary Disease 2014

Seemungal

Wedzicha

2015

Am J Respir Crit Care Med

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Section: Genetic Predispositionmentioning

confidence: 99%

“…This might indicate the need for larger studies better powered to detect rare variants, but which might also be capable of investigating interactions between genes and smoking (56). It is also possible, as the authors point out that susceptibility to COPD is determined by multiple rather than just a few gene (57).…”

Section: Genetic Predispositionmentioning

confidence: 99%

Update in Chronic Obstructive Pulmonary Disease 2014

Seemungal

Wedzicha

2015

Am J Respir Crit Care Med

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“…1353-1363), Qiao and colleagues attempted to discover rare susceptibility variants for an extreme COPD phenotype (severe disease of early onset), which may be influenced by rare coding variants with large effects. The investigators first conducted whole-exome sequencing to identify rare variants in 347 members of 49 extended pedigrees in the Boston Early-Onset COPD (EOCOPD) Study (11). They then conducted a segregation analysis, which identified 69 genes with rare deleterious variants that segregated in at least two pedigrees in the EOCOPD Study.…”

mentioning

confidence: 99%

“…In addition to attempting to identify rare susceptibility variants in novel genes, Qiao and colleagues tried to discover rare variants in known candidate genes for COPD or lung function (11). Supportive but nondefinitive evidence for such rare variants was shown for some candidate genes, including FAM13A and CCDC38.…”

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confidence: 99%

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The Advent of High-Throughput Sequencing Studies of Chronic Obstructive Pulmonary Disease

Ortega

Celedón

2016

Am J Respir Crit Care Med

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Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults

et al. 2023

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ImportancePulmonary fibrosis (PF) is characterized by progressive scarring of lung tissue and poor survival. Racial and ethnic minority populations face the greatest risk of morbidity and mortality from disparities impacting respiratory health, but the pattern of age at clinically relevant outcomes across diverse racial and ethnic populations with PF is unknown.ObjectiveTo compare the age at PF-related outcomes and the heterogeneity in survival patterns among Hispanic, non-Hispanic Black, and non-Hispanic White participants.Design, Setting, and ParticipantsThis cohort study included adult patients with a PF diagnosis and used data from prospective clinical registries: the Pulmonary Fibrosis Foundation Registry (PFFR) for the primary cohort and registries from 4 geographically distinct tertiary hospitals in the US for the external multicenter validation (EMV) cohort. Patients were followed between January 2003 and April 2021.ExposuresRace and ethnicity comparisons between Black, Hispanic, and White participants with PF.Main Outcomes and MeasuresAge and sex distribution of participants were measured at the time of study enrollment. All-cause mortality and age at PF diagnosis, hospitalization, lung transplant, and death were assessed in participants over 14 389 person-years. Differences between racial and ethnic groups were compared using Wilcoxon rank sum tests, Bartlett 1-way analysis of variance, and χ2 tests, and crude mortality rates and rate ratios were assessed across racial and ethnic categories using Cox proportional hazards regression models.ResultsIn total, 4792 participants with PF were assessed (mean [SD] age, 66.1 [11.2] years; 2779 [58.0%] male; 488 [10.2%] Black, 319 [6.7%] Hispanic, and 3985 [83.2%] White); 1904 were in the PFFR and 2888 in the EMV cohort. Black patients with PF were consistently younger than White patients (mean [SD] age at baseline, 57.9 [12.0] vs 68.6 [9.6] years; P &lt; .001). Hispanic and White patients were predominantly male (Hispanic: PFFR, 73 of 124 [58.9%] and EMV, 109 of 195 [55.9%]; and White: PFFR, 1090 of 1675 [65.1%] and EMV, 1373 of 2310 [59.4%]), while Black patients were less likely to be male (PFFR, 32 of 105 [30.5%] and EMV, 102 of 383 [26.6%]). Compared with White patients, Black patients had a lower crude mortality rate ratio (0.57 [95% CI, 0.31-0.97), but for Hispanic patients, the mortality rate ratio was similar to that of White patients (0.89; 95% CI, 0.57-1.35). Mean (SD) hospitalization events per person were highest among Black patients compared with Hispanic and White patients (Black: 3.6 [5.0]; Hispanic, 1.8 [1.4]; and White, 1.7 [1.3]; P &lt; .001). Black patients were consistently younger than Hispanic and White patients at first hospitalization (mean [SD] age: Black, 59.4 [11.7] years; Hispanic, 67.5 [9.8] years; and White, 70.0 [9.3] years; P &lt; .001), lung transplant (Black, 58.6 [8.6] years; Hispanic, 60.5 [6.1] years; and White, 66.9 [6.7] years; P &lt; .001), and death (Black, 68.7 [8.4] years; Hispanic, 72.9 [7.6] years; and White, 73.5 [8.7] years; P &lt; .001). These findings remained consistent in the replication cohort and in sensitivity analyses within prespecified deciles of age groups.Conclusions and RelevanceIn this cohort study of participants with PF, racial and ethnic disparities, especially among Black patients, were found in PF-related outcomes, including earlier onset of death. Further research is essential to identify and mitigate the underlying responsible factors.

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Exome Sequencing Analysis in Severe, Early-Onset Chronic Obstructive Pulmonary Disease

Abstract: Rare deleterious coding variants may increase risk for COPD, but multiple genes likely contribute to COPD susceptibility.

Cited by 45 publications

References 48 publications

Update in Chronic Obstructive Pulmonary Disease 2014

Update in Chronic Obstructive Pulmonary Disease 2014

The Advent of High-Throughput Sequencing Studies of Chronic Obstructive Pulmonary Disease

Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults

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