Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody-associated vasculitis characterized by the manifestation of asthma and eosinophilia in the early phases. Currently, it is not well understood how underlying genetic risk factors affect EGPA and its comorbidity. To address this question, we aim to identify novel genetic associations with EGPA and investigating their pleiotropy with molecular traits. We conducted a genome-wide association study (GWAS) in a discovery cohort combining two independent studies by meta-analysis. The combined study generated the largest GWAS of EGPA to date (829 cases and 9,586 controls). We performed replication in an independent cohort from European ancestry (99 cases and 1,680 controls). In current study, we identified and formally replicated a novel genome-wide significant association with EGPA in SSH2 locus. In the full meta-analysis combining our discovery and validation cohort, we also identified an additional genome-wide significant association in RUNX1 locus. We found significant evidence that the EGPA association in SSH2 locus colocalizes with trans-Quantitative Trait Loci (QTLs) affecting DNA methylation of CpG sites in IL5RA (a biological target of anti-IL5 therapy for EGPA) and in LYN (a tyrosine kinase interacting with IL5RA), which are also observed in asthmatics. Our findings provide new targets for future functional studies to elucidate pathogenesis of EGPA.
Neural manifolds that orchestrate walking and stopping
Walking, stopping and maintaining posture are essential motor behaviors, yet the underlying neural processes remain poorly understood. Here, we investigate neural activity behind locomotion and