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Genome-Wide Association Study of a Validated Case Definition of Gulf War Illness in a Population-Representative Sample

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Final rept. 1 Sep 2011-31 Aug 2013

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The specific aim of this study was to perform gene expression profiling and group comparison analyses of differential gene expression in RNA-stabilized blood samples of the approximately 150 veterans meeting the Factor case definition and Gulf War-era veteran controls. From the banked blood samples collected previously and stored frozen at -80 C in PAXgene tubes from 2 population subsamples of Gulf War veteran cases and controls, we were able to obtain sufficient high quality peripheral blood mononuclear cell PBMC RNA from 142. Our Genomics Core Laboratory performed Next Generation Transcriptome Sequencing RNA-Seq, using Illumina s multiplexing mRNA-Seq to generate full sequence libraries from the poly-A tailed RNA to a read depth of 30 million reads. Bioinformatics analyses for replicable differences in the expression levels among the 4 clinical groups were completed with the Dozmorov method to test for multiple comparisons-corrected group differences. In the tests for differentially expressed single target genes, no significant group differences were found, but the second stage using Ingenuity Pathway Analysis to test for common regulator genes identified 6 transcription regulators whose downstream target genes differed between syndrome group 2 and controls in the Developmental subsample and the Replication subsample. Most noteworthy was the finding of apparent instability in expression of the STAT3 regulatory oncogene, which, if confirmed, could explain increased rates of brain cancer in Gulf War veterans. Future research for a Gulf War illness diagnostic test should employ methods, such as pharmacologic stimulation and analysis of pure cell types, to reduce high background variability of gene expression in peripheral blood cells.

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  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

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