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, Yuan Zhou

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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.

Original languageEnglish
Article number5641
JournalNature Communications
Volume12
Issue1
Pages (from-to)5641
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - Sept 2021

Fingerprint

Dive into the research topics of 'Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases'. Together they form a unique fingerprint.

Cite this