Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysis
Abstract Aims Observational research has identified links between micronutrient levels and chronic liver disease. However, the lack of randomized controlled experiments has impeded the ability to establish a cause‐and‐effect connection regarding micronutrients and cirrhosis of the liver. This Mendel...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-09-01
|
| Series: | Portal Hypertension & Cirrhosis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/poh2.90 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850265413658607616 |
|---|---|
| author | Junlong Lin Jialin Chen Zhichao Li Baifeng Qian Yunpeng Hua |
| author_facet | Junlong Lin Jialin Chen Zhichao Li Baifeng Qian Yunpeng Hua |
| author_sort | Junlong Lin |
| collection | DOAJ |
| description | Abstract Aims Observational research has identified links between micronutrient levels and chronic liver disease. However, the lack of randomized controlled experiments has impeded the ability to establish a cause‐and‐effect connection regarding micronutrients and cirrhosis of the liver. This Mendelian randomization (MR) analysis aimed to examine the causal impact of micronutrients on liver cirrhosis. Methods We selected genetic instrumental variables related to 12 micronutrients from genome‐wide studies on individuals of European descent, covering an array of over 9,851,867 single nucleotide polymorphisms and 460,351 participants. Data from patients with cirrhosis in the FinnGen database (https://www.finngen.fi/fi) were used. A two‐sample MR approach was employed to establish genetically causal estimates. Primary analyses used random effects and inverse variance weighted (IVW) methods, with additional sensitivity analyses for validation. MR–Egger intercept analysis and Cochran's Q test assessed horizontal pleiotropy and heterogeneity. Furthermore, multivariable Mendelian randomization (MVMR) was conducted to address potential confounding variables. Results IVW and weighted median methods showed that most micronutrients included were not significantly associated with a genetic susceptibility to liver cirrhosis. However, MR analysis demonstrated a significant association between circulating vitamin D levels and a reduced risk of liver cirrhosis (odds ratio IVW = 0.53, p < 0.010). The MR–Egger intercept showed no evidence of horizontal pleiotropy (p = 0.178), whereas Cochran's Q test found no heterogeneity (p = 0.799). Furthermore, MVMR analysis confirmed vitamin D was identified as a factor that independently mitigates the risk of liver cirrhosis. Conclusion This research constitutes the most comprehensive MR investigation in this field, providing evidence supporting a protective link between circulating vitamin D levels and cirrhosis incidence. It suggests that maintaining sufficient vitamin D could be a cost‐effective strategy for early intervention in liver cirrhosis. |
| format | Article |
| id | doaj-art-34a8eca97ad94557897c14cbec50dc52 |
| institution | OA Journals |
| issn | 2770-5838 2770-5846 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Portal Hypertension & Cirrhosis |
| spelling | doaj-art-34a8eca97ad94557897c14cbec50dc522025-08-20T01:54:26ZengWileyPortal Hypertension & Cirrhosis2770-58382770-58462024-09-013316017010.1002/poh2.90Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysisJunlong Lin0Jialin Chen1Zhichao Li2Baifeng Qian3Yunpeng Hua4Department of Liver Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong ChinaDepartment of Liver Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong ChinaDepartment of Liver Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong ChinaDepartment of Liver Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong ChinaDepartment of Liver Surgery, The First Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong ChinaAbstract Aims Observational research has identified links between micronutrient levels and chronic liver disease. However, the lack of randomized controlled experiments has impeded the ability to establish a cause‐and‐effect connection regarding micronutrients and cirrhosis of the liver. This Mendelian randomization (MR) analysis aimed to examine the causal impact of micronutrients on liver cirrhosis. Methods We selected genetic instrumental variables related to 12 micronutrients from genome‐wide studies on individuals of European descent, covering an array of over 9,851,867 single nucleotide polymorphisms and 460,351 participants. Data from patients with cirrhosis in the FinnGen database (https://www.finngen.fi/fi) were used. A two‐sample MR approach was employed to establish genetically causal estimates. Primary analyses used random effects and inverse variance weighted (IVW) methods, with additional sensitivity analyses for validation. MR–Egger intercept analysis and Cochran's Q test assessed horizontal pleiotropy and heterogeneity. Furthermore, multivariable Mendelian randomization (MVMR) was conducted to address potential confounding variables. Results IVW and weighted median methods showed that most micronutrients included were not significantly associated with a genetic susceptibility to liver cirrhosis. However, MR analysis demonstrated a significant association between circulating vitamin D levels and a reduced risk of liver cirrhosis (odds ratio IVW = 0.53, p < 0.010). The MR–Egger intercept showed no evidence of horizontal pleiotropy (p = 0.178), whereas Cochran's Q test found no heterogeneity (p = 0.799). Furthermore, MVMR analysis confirmed vitamin D was identified as a factor that independently mitigates the risk of liver cirrhosis. Conclusion This research constitutes the most comprehensive MR investigation in this field, providing evidence supporting a protective link between circulating vitamin D levels and cirrhosis incidence. It suggests that maintaining sufficient vitamin D could be a cost‐effective strategy for early intervention in liver cirrhosis.https://doi.org/10.1002/poh2.90liver cirrhosisMendelian randomizationmicronutrientvitamin D |
| spellingShingle | Junlong Lin Jialin Chen Zhichao Li Baifeng Qian Yunpeng Hua Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysis Portal Hypertension & Cirrhosis liver cirrhosis Mendelian randomization micronutrient vitamin D |
| title | Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysis |
| title_full | Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysis |
| title_fullStr | Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysis |
| title_full_unstemmed | Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysis |
| title_short | Appraising the causal effects of circulating micronutrients on liver cirrhosis: Evidence from large‐scale Mendelian randomization analysis |
| title_sort | appraising the causal effects of circulating micronutrients on liver cirrhosis evidence from large scale mendelian randomization analysis |
| topic | liver cirrhosis Mendelian randomization micronutrient vitamin D |
| url | https://doi.org/10.1002/poh2.90 |
| work_keys_str_mv | AT junlonglin appraisingthecausaleffectsofcirculatingmicronutrientsonlivercirrhosisevidencefromlargescalemendelianrandomizationanalysis AT jialinchen appraisingthecausaleffectsofcirculatingmicronutrientsonlivercirrhosisevidencefromlargescalemendelianrandomizationanalysis AT zhichaoli appraisingthecausaleffectsofcirculatingmicronutrientsonlivercirrhosisevidencefromlargescalemendelianrandomizationanalysis AT baifengqian appraisingthecausaleffectsofcirculatingmicronutrientsonlivercirrhosisevidencefromlargescalemendelianrandomizationanalysis AT yunpenghua appraisingthecausaleffectsofcirculatingmicronutrientsonlivercirrhosisevidencefromlargescalemendelianrandomizationanalysis |