{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:52:07Z","timestamp":1782377527840,"version":"3.54.5"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["K08 DK133640"],"award-info":[{"award-number":["K08 DK133640"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Michigan Department of Internal Medicine","award":["Discretionary Funds"],"award-info":[{"award-number":["Discretionary Funds"]}]},{"name":"HHS | National Institutes of Health","award":["R01 DK106621,R01 DK107904"],"award-info":[{"award-number":["R01 DK106621,R01 DK107904"]}]},{"name":"MBioFar"},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["K08 DK132312"],"award-info":[{"award-number":["K08 DK132312"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Michigan Genomics Initiative"},{"name":"HHS | National Institutes of Health","award":["R01 HS027431"],"award-info":[{"award-number":["R01 HS027431"]}]},{"name":"HHS | National Institutes of Health","award":["R01 DK125687,R01 DK118154,T32 DK062708"],"award-info":[{"award-number":["R01 DK125687,R01 DK118154,T32 DK062708"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,11,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Patients with inflammatory bowel disease (IBD) are at increased risk of\n              <jats:italic>Clostridioides difficile<\/jats:italic>\n              infection (CDI). Herein, we aimed to determine if genetic risk contributes to this observed association. We carried out a genome-wide association study (GWAS) analysis in the Michigan Genomics Initiative and the United Kingdom Biobank for CDI based on ICD codes and meta-analyzed these results with similar publicly accessible GWAS summary statistics from Finngen. Conditional and joint multi-SNP analyses were used to identify independent associations. Imputation of the human leukocyte antigen (HLA) region with fine mapping was used to try to identify causal HLA allele groups. Two-sample bidirectional Mendelian randomization (MR) was implemented to determine causal relationships between IBD and CDI. A total of 3,500 cases of CDI and 674,323 controls were meta-analyzed, revealing one genome-wide significant variant for CDI,\n              <jats:italic>HLA-C;LINC02571<\/jats:italic>\n              -rs3134745-C (\n              <jats:italic>P<\/jats:italic>\n              = 4.27E\u221208), which annotated to the major histocompatibility complex on chromosome 6. While fine mapping did not identify a statistically significant HLA allele group, there was a suggestive signal for\n              <jats:italic>HLA-B<\/jats:italic>\n              *35:01 (\n              <jats:italic>P<\/jats:italic>\n              = 4.74e\u221204). Using two-sample MR, genetically predicted IBD was associated with increased risk of CDI (MR Egger [odds ratio {OR} 1.16, 95% confidence interval {CI} 1.02\u20131.31]). Subset analysis revealed that risk was primarily driven by genetically predicted ulcerative colitis (MR Egger [OR 1.22, 95% CI 1.05\u20131.41]). These results highlight the importance of the host immune response in CDI pathogenesis, help explain the observed relationship between IBD and CDI, and open new avenues for targeted treatment of CDI in IBD.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>Data from this paper (i) provide reproducible evidence that susceptibility CDI is genetically mediated, (ii) highlight genetic risk as a mechanism for the increased risk of CDI in patients with inflammatory bowel disease, and (iii) point toward anti-interleukin-23 therapy as a common therapeutic strategy.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00567-24","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T13:00:20Z","timestamp":1729602020000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Genetic insight into the relationship between inflammatory bowel disease and\n            <i>Clostridioides difficile<\/i>\n            infection"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3914-9673","authenticated-orcid":true,"given":"Kelly C.","family":"Cushing-Damm","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annapurna","family":"Kuppa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmay","family":"Raut","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Oliveri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent L.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Vanderwerff","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Zawistowski","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9213-7850","authenticated-orcid":true,"given":"Krishna","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan, 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