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There are challenges “inherent” in studying the genetics of a complex disease, such as acute respiratory distress syndrome (ARDS). It is necessary to define each ARDS subgroup using considerably narrower definitions that better reflect the particular subgroup. ARDS consists of several phenotypic subgroups, and findings from one subgroup may not be applicable to another. By extension, different treatment therapies may be appropriate for each phenotypic subgroup. This article presents the findings of a small pilot case-control association study where the surfactant proteins were used as candidate genes in the study of ARDS. This article discusses the relevance of surfactant protein genes in ARDS as well as the significance of genetic variants associated with ARDS subgroups.