Primary sclerosing cholangitis causally affects kidney function decline : A Mendelian randomization study
© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd..
BACKGROUND AND AIM: The causal linkage between primary sclerosing cholangitis (PSC) and kidney function is unexplored despite their potential for long-term detrimental effects on kidney function.
METHODS: Two-sample summary-level Mendelian randomization (MR) study was conducted to identify the association between PSC and kidney function. The genetic variants were extracted from the PSC-specific multi-trait analyzed genome-wide association study (GWAS) of European ancestry. Summary-level data for kidney function traits, including estimated glomerular filtration rate (eGFR), annual eGFR decline, and chronic kidney disease (CKD), were obtained from the CKDGen consortium. Multiplicative random-effects inverse-variance weighted (MR-IVW), and a series of pleiotropy-robust analyses were performed to investigate the causal effects and ascertain their robustness.
RESULTS: Significant causal associations between genetically predicted PSC and kidney function traits were identified. Genetically predicted PSC was associated with decreased log-transformed eGFR (MR-IVW; beta = -0.41%; standard error [SE] = 0.02%; P < 0.001), increased rate of annual eGFR decline (MR-IVW; beta = 2.43%; SE = 0.18%; P < 0.001), and higher risk of CKD (MR-IVW; odds ratio = 1.07; 95% confidence interval = 1.06-1.08; P < 0.001). The main findings were supported by pleiotropy-robust analysis, including MR-Egger with bootstrapped error and weighted median.
CONCLUSIONS: Our study demonstrates that genetically predicted PSC is causally associated with kidney function impairment. Further studies are warranted to identify the underlying mechanisms.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
Journal of gastroenterology and hepatology - 39(2024), 1 vom: 19. Jan., Seite 185-192 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cho, Jeong Min [VerfasserIn] |
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| Links: |
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| Themen: |
Chronic kidney failure |
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| Anmerkungen: |
Date Completed 31.01.2024 Date Revised 31.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/jgh.16355 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362236933 |
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| 100 | 1 | |a Cho, Jeong Min |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Primary sclerosing cholangitis causally affects kidney function decline |b A Mendelian randomization study |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 31.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. | ||
| 520 | |a BACKGROUND AND AIM: The causal linkage between primary sclerosing cholangitis (PSC) and kidney function is unexplored despite their potential for long-term detrimental effects on kidney function | ||
| 520 | |a METHODS: Two-sample summary-level Mendelian randomization (MR) study was conducted to identify the association between PSC and kidney function. The genetic variants were extracted from the PSC-specific multi-trait analyzed genome-wide association study (GWAS) of European ancestry. Summary-level data for kidney function traits, including estimated glomerular filtration rate (eGFR), annual eGFR decline, and chronic kidney disease (CKD), were obtained from the CKDGen consortium. Multiplicative random-effects inverse-variance weighted (MR-IVW), and a series of pleiotropy-robust analyses were performed to investigate the causal effects and ascertain their robustness | ||
| 520 | |a RESULTS: Significant causal associations between genetically predicted PSC and kidney function traits were identified. Genetically predicted PSC was associated with decreased log-transformed eGFR (MR-IVW; beta = -0.41%; standard error [SE] = 0.02%; P < 0.001), increased rate of annual eGFR decline (MR-IVW; beta = 2.43%; SE = 0.18%; P < 0.001), and higher risk of CKD (MR-IVW; odds ratio = 1.07; 95% confidence interval = 1.06-1.08; P < 0.001). The main findings were supported by pleiotropy-robust analysis, including MR-Egger with bootstrapped error and weighted median | ||
| 520 | |a CONCLUSIONS: Our study demonstrates that genetically predicted PSC is causally associated with kidney function impairment. Further studies are warranted to identify the underlying mechanisms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic kidney failure | |
| 650 | 4 | |a Glomerular filtration rate | |
| 650 | 4 | |a Kidney function tests | |
| 650 | 4 | |a Mendelian randomization analysis | |
| 650 | 4 | |a Primary sclerosing cholangitis | |
| 700 | 1 | |a Koh, Jung Hun |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Seong Geun |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Soojin |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yaerim |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Semin |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kwangsoo |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yong Chul |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Seung Seok |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Hajeong |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jung Pyo |e verfasserin |4 aut | |
| 700 | 1 | |a Joo, Kwon Wook |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Chun Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yon Su |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Dong Ki |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Sehoon |e verfasserin |4 aut | |
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