Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease
Background Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD).Aim To test...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-11-01
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| Series: | BMJ Open Gastroenterology |
| Online Access: | https://bmjopengastro.bmj.com/content/10/1/e001141.full |
| _version_ | 1797371497113714688 |
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| author | William A Faubion Rodney D Newberry Ming-Hsi Wang Jessica J Friton Laura E Raffals Jonathan A Leighton Shabana F Pasha Michael F Picco Kelly Monroe Billy D Nix |
| author_facet | William A Faubion Rodney D Newberry Ming-Hsi Wang Jessica J Friton Laura E Raffals Jonathan A Leighton Shabana F Pasha Michael F Picco Kelly Monroe Billy D Nix |
| author_sort | William A Faubion |
| collection | DOAJ |
| description | Background Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD).Aim To test whether PRS indicates PSC risk in patients with IBD.Materials and methods Mayo Clinic and Washington University at St Louis IBD cohorts were used to test our hypothesis. PRS was modelled through the published PSC loci and weighted with their corresponding effect size. Logistic regression was applied to predict the PSC risk.Results In total, 63 (5.6%) among 1130 patients with IBD of European ancestry had PSC. Among 381 ulcerative colitis (UC), 12% had PSC; in contrast to 1.4% in 761 Crohn disease (CD). Compared with IBD alone, IBD-PSC had significantly higher PRS (PSC risk: 3.0% at the lowest PRS quartile vs 7.2% at the highest PRS quartile, Ptrend =.03). In IBD subphenotypes subgroup analysis, multivariate analysis shows that UC-PSC is associated with more extensive UC disease (OR, 5.60; p=0.002) and younger age at diagnosis (p=0.02). In CD, multivariate analysis suggests that CD-PSC is associated with colorectal cancer (OR, 50; p=0.005).Conclusions We found evidence that patients with IBD with PSC presented with a clinical course difference from that of patients with IBD alone. PRS can influence PSC risk in patients with IBD. Once validated in an independent cohort, this may help identify patients with the highest likelihood of developing PSC. |
| first_indexed | 2024-03-08T18:21:05Z |
| format | Article |
| id | doaj.art-785e6c5034e74ee48c0a9aa92cccda9c |
| institution | Directory Open Access Journal |
| issn | 2054-4774 |
| language | English |
| last_indexed | 2024-03-08T18:21:05Z |
| publishDate | 2023-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Gastroenterology |
| spelling | doaj.art-785e6c5034e74ee48c0a9aa92cccda9c2023-12-30T22:30:07ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742023-11-0110110.1136/bmjgast-2023-001141Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel diseaseWilliam A Faubion0Rodney D Newberry1Ming-Hsi Wang2Jessica J Friton3Laura E Raffals4Jonathan A Leighton5Shabana F Pasha6Michael F Picco7Kelly Monroe8Billy D Nix9Mayo Clinic, Rochester, Minnesota, USAWashington University in St Louis, St Louis, Missouri, USAMayo Clinic, Mankato, Minnesota, USAMayo Clinic, Rochester, Minnesota, USAMayo Clinic, Rochester, Minnesota, USAMayo Clinic Scottsdale, Scottsdale, Arizona, USAMayo Clinic Scottsdale, Scottsdale, Arizona, USAMayo Clinic in Florida, Jacksonville, Florida, USAWashington University in St Louis, St Louis, Missouri, USAWashington University in St Louis, St Louis, Missouri, USABackground Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD).Aim To test whether PRS indicates PSC risk in patients with IBD.Materials and methods Mayo Clinic and Washington University at St Louis IBD cohorts were used to test our hypothesis. PRS was modelled through the published PSC loci and weighted with their corresponding effect size. Logistic regression was applied to predict the PSC risk.Results In total, 63 (5.6%) among 1130 patients with IBD of European ancestry had PSC. Among 381 ulcerative colitis (UC), 12% had PSC; in contrast to 1.4% in 761 Crohn disease (CD). Compared with IBD alone, IBD-PSC had significantly higher PRS (PSC risk: 3.0% at the lowest PRS quartile vs 7.2% at the highest PRS quartile, Ptrend =.03). In IBD subphenotypes subgroup analysis, multivariate analysis shows that UC-PSC is associated with more extensive UC disease (OR, 5.60; p=0.002) and younger age at diagnosis (p=0.02). In CD, multivariate analysis suggests that CD-PSC is associated with colorectal cancer (OR, 50; p=0.005).Conclusions We found evidence that patients with IBD with PSC presented with a clinical course difference from that of patients with IBD alone. PRS can influence PSC risk in patients with IBD. Once validated in an independent cohort, this may help identify patients with the highest likelihood of developing PSC.https://bmjopengastro.bmj.com/content/10/1/e001141.full |
| spellingShingle | William A Faubion Rodney D Newberry Ming-Hsi Wang Jessica J Friton Laura E Raffals Jonathan A Leighton Shabana F Pasha Michael F Picco Kelly Monroe Billy D Nix Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease BMJ Open Gastroenterology |
| title | Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease |
| title_full | Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease |
| title_fullStr | Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease |
| title_full_unstemmed | Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease |
| title_short | Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease |
| title_sort | polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease |
| url | https://bmjopengastro.bmj.com/content/10/1/e001141.full |
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