bioRxivGeneticsPreprint
A genome-wide genetic pleiotropy approach identified shared loci between multiple system atrophy and inflammatory bowel disease
Alexey A. ShadriniD, Sören MuchaiD, David EllinghausiD, Mary B. MakariousiD, Cornelis BlauwendraatiD, Ashwin Ashok Kumar SreelathaiD, Antonio Heras‐GarviniD, Jinhui DingiD, Monia Benhamed HammeriD, Alexandra Foubert‐SamieriD, Wassilios G. MeissneriD, Olivier RascoliD, Anne Pavy‐Le TraoniD, Oleksandr FreiiD, Kevin Sean O’ConnelliD, Shahram BahramiiD, Stefan SchreiberiD, Wolfgang LiebiD, Martina Müller‐NurasyidiD, Andreas Arnold, Georg HomuthiD, Carsten Oliver SchmidtiD, Markus Maria NötheniD, Per HoffmanniD, Christian GiegeriD, , Manu SharmaiD
Abstract
We aimed to identify shared genetic background between multiple system atrophy (MSA) and autoimmune diseases by using the conjFDR approach. Our study showed significant genetic overlap between MSA and inflammatory bowel disease and identified DENND1B, C7, and RSP04 loci, which are linked to significant changes in methylation or expression levels of adjacent genes. We obtained evidence of enriched heritability involving immune/digestive categories. Finally, an MSA mouse model showed dysregulation of the C7 gene in the degenerating midbrain compared to wildtype mice. The results identify novel molecular mechanisms and implicate immune and gut dysfunction in MSA pathophysiology.
- organism: mouse
- assay: DNA methylation
- research focus: GWAS / association mapping
- approach: statistical model
- Citations
- 0
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