{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:34:54Z","timestamp":1787582094776,"version":"build-2736575974"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Critical illness syndromes, such as sepsis and acute respiratory distress syndrome (ARDS), are characterized by substantial clinical heterogeneity and remain major causes of morbidity and mortality worldwide. Increasing evidence suggests that genetic variation contributes to susceptibility, disease severity, and clinical outcomes in critically ill patients. However, the molecular mechanisms linking genetic predisposition to the pathophysiology of sepsis and ARDS remain incompletely understood. In this review, we evaluated genetic associations reported in sepsis and ARDS, including 13 genome-wide studies identifying 19 unique single-nucleotide polymorphisms (SNPs) across 17 distinct genomic loci, as well as 21 meta-analyses of candidate-gene studies identifying 21 SNPs across 16 genes. The identified variants were primarily associated with pathways involved in pathogen recognition, immune and inflammatory signaling, leukocyte recruitment, and endothelial dysfunction. Collectively, these findings support a polygenic basis for susceptibility to critical illness and highlight several biologically relevant pathways that may contribute to sepsis and ARDS pathogenesis. Improved understanding of the functional consequences of these variants may facilitate the identification of potential therapeutic targets and support the development of precision-guided approaches to critical care.<\/jats:p>","DOI":"10.3389\/fphar.2026.1864880","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:51:48Z","timestamp":1787579508000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic associations in sepsis and ARDS"],"prefix":"10.3389","volume":"17","author":[{"given":"Jonathan J.","family":"Moroniti","sequence":"first","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poorna Manappurathu","family":"Rameshchandran","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Labuda","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]},{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Chandy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]},{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]},{"name":"Lawson Health Research Institute, London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Leligdowicz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]},{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]},{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University","place":["London, ON, Canada"]},{"name":"Lawson Health Research Institute, London Health Sciences Centre","place":["London, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.3390\/cells10092319","article-title":"Induced pluripotent stem cells (iPSCs)-Roles in regenerative therapies, disease modelling and drug screening","volume":"10","author":"Aboul-Soud","year":"2021","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1002\/jlb.66.4.562","article-title":"Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease","volume":"66","author":"Abraham","year":"1999","journal-title":"J. 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