TY - JOUR
T1 - Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease
AU - Wang, Ming Hsi
AU - Friton, Jessica J.
AU - Raffals, Laura E.
AU - Leighton, Jonathan A.
AU - Pasha, Shabana F.
AU - Picco, Michael F.
AU - Monroe, Kelly
AU - Nix, Billy D.
AU - Newberry, Rodney D.
AU - Faubion, William A.
N1 - Publisher Copyright:
© 2023 BMJ Publishing Group. All rights reserved.
PY - 2023/10/13
Y1 - 2023/10/13
N2 - 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, P trend =.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.
AB - 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, P trend =.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.
KW - genetics
KW - inflammatory bowel disease
KW - primary sclerosing cholangitis
UR - http://www.scopus.com/inward/record.url?scp=85175249213&partnerID=8YFLogxK
U2 - 10.1136/bmjgast-2023-001141
DO - 10.1136/bmjgast-2023-001141
M3 - Article
C2 - 37832963
AN - SCOPUS:85175249213
SN - 2054-4774
VL - 10
JO - BMJ Open Gastroenterology
JF - BMJ Open Gastroenterology
IS - 1
M1 - e001141
ER -