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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Acute Lung Injury, Adult, African Continental Ancestry Group, Cohort Studies, European Continental Ancestry Group, Female, Genetic Association Studies, Genetic Predisposition to Disease, Haplotypes, Humans, I-kappa B Proteins, Interleukin-1 Receptor-Associated Kinases, Interleukin-10, Interleukin-6, Male, Middle Aged, NF-KappaB Inhibitor alpha, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Prospective Studies, Reproducibility of Results, Severity of Illness Index, Vascular Endothelial Growth Factor A, Wounds and Injuries, Young Adult.
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Does sNP-set analysis replicate acute lung injury genetic risk factors? Context: We used a gene - based replication strategy to test the reproducibility of prior acute lung injury (ALI) candidate gene associations. We phenotyped 474 patients from a prospective severe trauma cohort study for ALI. Genomic DNA from subjects' blood was genotyped using the IBC chip, a multiplex single nucleotide polymorphism (SNP) array. Results were filtered for 25 candidate genes selected using prespecified literature search criteria and present on the IBC platform. For each gene, we grouped SNPs according to haplotype blocks and tested the joint effect of all SNPs on susceptibility to ALI using the SNP-set kernel association test. Results were compared to single SNP analysis of the candidate SNPs. Analyses were separate for genetically determined ancestry (African or European). We identified 4 genes in African ancestry and 2 in European ancestry trauma subjects which replicated their associations with ALI. Ours is the first replication of IL6, IL10, IRAK3, and VEGFA associations in non-European populations with ALI. Only one gene - VEGFA - demonstrated association with ALI in both ancestries, with distinct haplotype blocks in each ancestry driving the association. We also report the association between trauma-associated ALI and NFKBIA in European ancestry subjects.
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Prior ALI genetic associations are reproducible and replicate in a trauma cohort. Kernel - based SNP-set analysis is a more powerful method to detect ALI association than single SNP analysis, and thus may be more useful for replication testing. Further, gene-based replication can extend candidate gene associations to diverse ethnicities. Final Decision: yes