Genetic Risks for ALI in ARDSNet and the iSPAAR Consortium

This GWAS sub-study [phs000686](study.cgi?study_id=phs000686) contains genotype and selected phenotype of subjects available from the [phs000631](study.cgi?study_id=phs000631) study. Summary level phenotypes for the "ARDSnet and the iSPAAR Consortium: Genetic Studies" study participants can be viewed at the top-level study page [phs000631](study.cgi?study_id=phs000631) ARDSNet iSPAAR cohort. Individual level phenotype data and molecular data for all ARDSnet and the "iSPAAR Consortium: Genetic Studies" top-level study and sub-studies are available by requesting Authorized Access to the "ARDSnet and the iSPAAR Consortium: Genetic Studies" [phs000631](study.cgi?study_id=phs000631) study.

The primary goal of this study is to identify genetic factors that alter the risk of individuals for developing acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), a condition characterized by severe lung inflammation and an inability to maintain adequate oxygenation levels and high mortality. We employed genome wide association studies (GWAS) comparing a group of patients with ARDS (n=1072) with a group of critically ill patients at-risk for the development of ARDS (n=1124).

Samples and phenotype information were acquired from existing cohorts assembled as part of the iSPAAR (Identification of SNPs Predisposing to Altered ALI Risk) consortium, a multi-institutional NHLBI-funded study (RC2 HL101779) focused on the identification of genetic risks for ALI and related outcomes. Cases of established ALI in iSPAAR include subjects from the Molecular Epidemiology of Acute Respiratory Distress (MEA) Study [1] enrolled at the Massachusetts General Hospital, and from the ARDSNet consortium (http://www.ardsnet.org/), an NHLBI-funded clinical research network that performs randomized clinical trials in ARDS. We employed ARDS cases from ARDSNet Fluid and Catheter Treatment Trial (FACTT)[2], the EDEN-OMEGA studies[3,4], and the Albuterol for the Treatment of ALI (ALTA) study[5]. Controls at-risk for ALI who did not develop ALI during their hospital course were obtained from the MEA study[1]. We limited genotyping to subjects of European descent and who were ? 18 years of age. The genetic variants most strongly associated (upper 1st percentile) with ALI susceptibility from this GWAS are being validated through genotyping of the variants using a custom genotyping chip in a separate set of ALI cases and "at-risk" control subjects in a study design that mirrors the GWAS. Genotypes obtained from this validation study will be available through collaboration with Dr. Wurfel and Dr. Christiani, the principal investigators on this study. Of note, a subset of these subjects were also included in the NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Acute Lung Injury), phs000334, for which whole exome sequence and exome chip genotyping were obtained. In this project, additional cases of ARDS were obtained from the Validating Acute Lung Injury biomarkers for Diagnosis (VALID) study led by Dr. Lorraine Ware of Vanderbilt University.