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Epigenome-Wide Association Study of Survival in Acute Respiratory Distress Syndrome
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A1948 - Epigenome-Wide Association Study of Survival in Acute Respiratory Distress Syndrome
Author Block: Y. Guo1, R. Zhang2, Z. Zhu1, S. Shen1, P. Tejera1, L. Su1, D. C. Christiani1; 1Environmental Health, Harvard T.H.Chan School of Public Health, Boston, MA, United States, 2Biostatistics, Nanjing Medical University, Nanjing, China.
Rationale: DNA methylation, a crucial epigenetic modification of the genome, may represent a potential biomarker as well as therapeutic target. We performed an epigenome-wide association study (EWAS) between DNA methylation and 28-day overall survival time in Acute Respiratory Distress Syndrome (ARDS) patients based on Berlin criteria, to identify CpG probes that can be used as potential prognostic biomarkers. To the best of our knowledge, this is the first genome-wide epigenetic study in ARDS patients. Methods: We collected 185 patients from Molecular Epidemiology of ARDS (MEARDS) prospectively enrolled from ICU. DNA was extracted from whole blood. Patients were randomly separated into two batches and DNA methylation was measured using Illumina Infinium HumanMethylation450 BeadChips. Association between each methylation probe and 28-day overall survival was evaluated by Cox models in each batches separately, with adjustment for clinical information. Multiple testing corrections were performed using false positive rate (FDR). Results: We fitted Cox models with 28-day overall survival of patients as a dependent variable and methylation status as a predictor, with age, gender and APACHE score as covariates. We identified 5 loci that are significantly related to survival status after multiple testing corrections in each of the two batches of patients. Results were described as hazard ratio (HR) and 95%CI per 1% methylation increment, as well as visualizing evaluations such as q-q plot, Manhattan plot and volcano plot. Conclusions: We performed the first Epigenome-wide Association Study of ARDS patient around world and revealed that 5 methylation loci were associated with ARDS prognosis. Some of them are located at genes related to allergic inflammation and allergic airway inflammation.
Author Block: Y. Guo1, R. Zhang2, Z. Zhu1, S. Shen1, P. Tejera1, L. Su1, D. C. Christiani1; 1Environmental Health, Harvard T.H.Chan School of Public Health, Boston, MA, United States, 2Biostatistics, Nanjing Medical University, Nanjing, China.
Rationale: DNA methylation, a crucial epigenetic modification of the genome, may represent a potential biomarker as well as therapeutic target. We performed an epigenome-wide association study (EWAS) between DNA methylation and 28-day overall survival time in Acute Respiratory Distress Syndrome (ARDS) patients based on Berlin criteria, to identify CpG probes that can be used as potential prognostic biomarkers. To the best of our knowledge, this is the first genome-wide epigenetic study in ARDS patients. Methods: We collected 185 patients from Molecular Epidemiology of ARDS (MEARDS) prospectively enrolled from ICU. DNA was extracted from whole blood. Patients were randomly separated into two batches and DNA methylation was measured using Illumina Infinium HumanMethylation450 BeadChips. Association between each methylation probe and 28-day overall survival was evaluated by Cox models in each batches separately, with adjustment for clinical information. Multiple testing corrections were performed using false positive rate (FDR). Results: We fitted Cox models with 28-day overall survival of patients as a dependent variable and methylation status as a predictor, with age, gender and APACHE score as covariates. We identified 5 loci that are significantly related to survival status after multiple testing corrections in each of the two batches of patients. Results were described as hazard ratio (HR) and 95%CI per 1% methylation increment, as well as visualizing evaluations such as q-q plot, Manhattan plot and volcano plot. Conclusions: We performed the first Epigenome-wide Association Study of ARDS patient around world and revealed that 5 methylation loci were associated with ARDS prognosis. Some of them are located at genes related to allergic inflammation and allergic airway inflammation.
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