DOI: 10.1101/491837Dec 10, 2018Paper

Genetically distinct clinical subsets, and associations with asthma and eosinophil abundance, within Eosinophilic Granulomatosis with Polyangiitis

BioRxiv : the Preprint Server for Biology
Paul A LyonsKenneth G C Smith


Eosinophilic granulomatosis with polyangiitis (EGPA: formerly Churg-Strauss syndrome) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasm antibodies (ANCA) specific for myeloperoxidase (MPO). We performed a genome-wide association study (GWAS) of EGPA, testing 7.5 million genetic variants in 684 cases and 6,838 controls. Case-control analyses were performed for EGPA as a whole, and stratified by ANCA. To increase power, we used a conditional false discovery rate method to leverage findings from GWASs of related phenotypes. In total, 11 variants were associated with EGPA, two specifically with ANCA-negative EGPA, and one (HLA-DQ) with MPO+ANCA EGPA. Many variants were associated with asthma, eosinophilic and immune-mediated diseases and, strikingly, nine were associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia underlies EGPA susceptibility. We demonstrate that EGPA comprises two genetically and clinically distinct syndromes, with ANCA-negative EGPA genetically more similar to asthma. MPO+ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an MHC association with MP...Continue Reading

Related Concepts

Autoimmune Diseases
Churg-Strauss Syndrome
Disease Susceptibility
Gram-Negative Bacteria
HLA-DQ Antigens

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