Study characteristics were compared between patients who developed ARDS and those who did not using the χ2 test for categorical variables and Wilcoxon rank-sum test for continuous variables. In the primary analyses, multivariable logistic regression was used to determine the association of genetically determined blood type A1 versus O with moderate or severe ARDS risk, adjusting for a prespecified list of potential confounders and population stratification. Population stratification was determined via principal component analyses and all multivariable models were adjusted for principal components 1 through 4. Our primary comparison was between ABO blood type A1 and O because it is unclear whether rarer blood types exhibit a phenotype closer to A1 or O, and we are underpowered to evaluate such differences. We used moderate to severe ARDS as the primary outcome because these patients are more likely to have diffuse alveolar damage, the pathological correlate to ARDS, as their underlying pathology (49). We also prespecified secondary analyses stratified by source of sepsis in the 2 sepsis cohorts. We tested for statistical interaction by source of sepsis, race, and mechanism of trauma using the likelihood ratio test. Biomarker concentrations were compared between blood types first in MESSI and PETROS separately using the Wilcoxon rank-sum test. We then combined the cohorts to conduct adjusted analyses using multivariable linear regression. For regression models, biomarker concentrations were first log-transformed to approximate a normal distribution. Biomarker concentrations were then compared between ARDS and no ARDS using the Wilcoxon rank-sum test followed by multivariable logistic regression adjusting for potential confounders. Multivariable logistic regression was also used to test the association of blood type and DIC, as well as blood type and EVLP recovery. A P value less than 0.05 was considered significant.

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