Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases

Yuanhao Yang, Hannah Musco, Steve Simpson-Yap, Zhihong Zhu, Ying Wang, Xin Lin, Jiawei Zhang, Bruce Taylor (), Jacob Gratten () and Yuan Zhou ()
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Yuanhao Yang: Mater Research, Translational Research Institute
Hannah Musco: Mater Research, Translational Research Institute
Steve Simpson-Yap: Menzies Institute for Medical Research, University of Tasmania
Zhihong Zhu: Institute for Molecular Bioscience, The University of Queensland
Ying Wang: Mater Research, Translational Research Institute
Xin Lin: Menzies Institute for Medical Research, University of Tasmania
Jiawei Zhang: the First Affiliated Hospital of Anhui Medical University
Bruce Taylor: Menzies Institute for Medical Research, University of Tasmania
Jacob Gratten: Mater Research, Translational Research Institute
Yuan Zhou: Menzies Institute for Medical Research, University of Tasmania

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract An 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.

Date: 2021
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DOI: 10.1038/s41467-021-25768-0

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