151431 - Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases.pdf (790.08 kB)
Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases
journal contribution
posted on 2023-05-21, 10:04 authored by Yang, Y, Musco, H, Simpson-Yap, S, Zhu, Z, Wang, Y, Lin, X, Zhang, J, Bruce TaylorBruce Taylor, Gratten, J, Yuan ZhouYuan ZhouAn epidemiological association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is well established, but whether this reflects a shared genetic aetiology, and whether consistent genetic relationships exist between MS and the two predominant IBD subtypes, ulcerative colitis (UC) and Crohn’s disease (CD), remains unclear. Here, we use large-scale genome-wide association study summary data to investigate the shared genetic architecture between MS and IBD overall and UC and CD independently. We find a significantly greater genetic correlation between MS and UC than between MS and CD, and identify three SNPs shared between MS and IBD (rs13428812), UC (rs116555563) and CD (rs13428812, rs9977672) in cross-trait meta-analyses. We find suggestive evidence for a causal effect of MS on UC and IBD using Mendelian randomization, but no or weak and inconsistent evidence for a causal effect of IBD or UC on MS. We observe largely consistent patterns of tissue-specific heritability enrichment for MS and IBDs in lung, spleen, whole blood and small intestine, and identify cell-type-specific enrichment for MS and IBDs in CD4+ T cells in lung and CD8+ cytotoxic T cells in lung and spleen. Our study sheds light on the biological basis of comorbidity between MS and IBD.
History
Publication title
Nature CommunicationsVolume
12Article number
5641Number
5641Pagination
1-12ISSN
2041-1723Department/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
Copyright 2021 the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open