Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Integrative omics provide biological and clinical insights into acute respiratory distress syndrome.

Authors: Du, Mulong; Garcia, Joe G N; Christie, Jason D; Xin, Junyi; Cai, Guoshuai; Meyer, Nuala J; Zhu, Zhaozhong; Yuan, Qianyu; Zhang, Zhengdong; Su, Li; Shen, Sipeng; Dong, Xuesi; Li, Hui; Hutchinson, John N; Tejera, Paula; Lin, Xihong; Wang, Meilin; Chen, Feng; Christiani, David C

Published In Intensive Care Med, (2021 07)

Abstract: PURPOSE: Acute respiratory distress syndrome (ARDS) is accompanied by a dysfunctional immune-inflammatory response following lung injury, including during coronavirus disease 2019 (COVID-19). Limited causal biomarkers exist for ARDS development. We sought to identify novel genetic susceptibility targets for ARDS to focus further investigation on their biological mechanism and therapeutic potential. METHODS: Meta-analyses of ARDS genome-wide association studies were performed with 1250 cases and 1583 controls in Europeans, and 387 cases and 387 controls in African Americans. The functionality of novel loci was determined in silico using multiple omics approaches. The causality of 114 factors potentially involved in ARDS development was assessed using Mendelian Randomization analysis. RESULTS: There was distinct genetic heterogeneity in ARDS between Europeans and African Americans. rs7967111 at 12p13.2 was functionally associated with ARDS susceptibility in Europeans (odds ratio = 1.38; P = 2.15 × 10-8). Expression of two genes annotated at this locus, BORCS5 and DUSP16, was dynamic but ultimately decreased during ARDS development, as well as downregulated in immune cells alongside COVID-19 severity. Causal inference implied that comorbidity of inflammatory bowel disease and elevated levels of C-reactive protein and interleukin-10 causally increased ARDS risk, while vitamin D supplementation and vasodilator use ameliorated risk. CONCLUSION: Our findings suggest a novel susceptibility locus in ARDS pathophysiology that implicates BORCS5 and DUSP16 as potentially acting in immune-inflammatory processes. This locus warrants further investigation to inform the development of therapeutic targets and clinical care strategies for ARDS, including those induced by COVID-19.

PubMed ID: 34032881 Exiting the NIEHS site

MeSH Terms: COVID-19*; Genome-Wide Association Study; Humans; Respiratory Distress Syndrome*/genetics; SARS-CoV-2; Whites/genetics

to Top