Principal Investigator: Dr Blanca Himes
University of Pennsylvania, PA, USATags: 40375, acute respiratory failure, critical-care, genetics/genotyping, GWAS, Pulmonary
Dr Michael Cho – Brigham and Womens Hospital, Boston, Massachusetts, USA
Acute respiratory failure (ARF) is a common cause of morbidity and mortality in critical illness. Severe ARF is associated with a mortality between 20% to 40%. Few genetics studies have been performed for ARF, and we do not fully understand how genes or the environment influence this disease. We aim to uncover risk determinants of ARF to improve its diagnosis and management. We will use genome-wide association study (GWAS) and gene-environment interaction analysis within the UK Biobank to: 1) identify genetic associations with severe ARF 2) evaluate gene-environment interactions with ARF. Completion of these aims will enhance our understanding of the pathophysiology of ARF.
New scope extension: We would like to maintain our current aims as originally proposed, but in light of our preliminary analyses, we would like to extend the scope of our proposal. Specifically, we would like to include a third aim: 3) compare genetic associations of various chronic pulmonary diseases (e.g., asthma, COPD, sarcoidosis) and assess their heritability. This change is due to the fact that there are few persons in UKBiobank with ARF, but among the categories of pulmonary diseases that are related to ARF, we have found that sarcoidosis has a reasonable sample size with some suggestive peaks. As we continue to work on Aims 1 and 2, we would like to better understand the genetic contribution to various chronic respiratory diseases and how the definitions according to ICD codes vs. self-report influence the results of GWAS. Doing so may help us pick best-case-scenario definitions of ARF and other diseases, and find out whether even if sample sizes are small and GWAS results for some diseases do not look as strong as for some traits with larger sample size, there still seems to be an underlying genetic contribution that could be measured.
Last updated Sep 16, 2019