Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
BMJ open gastroenterology - 10(2023), 1 vom: 11. Okt. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Ming-Hsi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Genetics |
|---|
| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 12.01.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1136/bmjgast-2023-001141 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363259279 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363259279 | ||
| 003 | DE-627 | ||
| 005 | 20240114234239.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/bmjgast-2023-001141 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1257.xml |
| 035 | |a (DE-627)NLM363259279 | ||
| 035 | |a (NLM)37832963 | ||
| 035 | |a (PII)e001141 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Ming-Hsi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.10.2023 | ||
| 500 | |a Date Revised 12.01.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a 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) | ||
| 520 | |a AIM: To test whether PRS indicates PSC risk in patients with IBD | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a inflammatory bowel disease | |
| 650 | 4 | |a primary sclerosing cholangitis | |
| 700 | 1 | |a Friton, Jessica J |e verfasserin |4 aut | |
| 700 | 1 | |a Raffals, Laura E |e verfasserin |4 aut | |
| 700 | 1 | |a Leighton, Jonathan A |e verfasserin |4 aut | |
| 700 | 1 | |a Pasha, Shabana F |e verfasserin |4 aut | |
| 700 | 1 | |a Picco, Michael F |e verfasserin |4 aut | |
| 700 | 1 | |a Monroe, Kelly |e verfasserin |4 aut | |
| 700 | 1 | |a Nix, Billy D |e verfasserin |4 aut | |
| 700 | 1 | |a Newberry, Rodney D |e verfasserin |4 aut | |
| 700 | 1 | |a Faubion, William A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t BMJ open gastroenterology |d 2014 |g 10(2023), 1 vom: 11. Okt. |w (DE-627)NLM253637635 |x 2054-4774 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2023 |g number:1 |g day:11 |g month:10 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1136/bmjgast-2023-001141 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2023 |e 1 |b 11 |c 10 | ||