Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis
Abstract Background Liver injury is associated with cholelithiasis, with changes in liver enzyme levels potentially influencing cholelithiasis risk. This study investigates the shared genetic basis between serum levels of four liver enzymes and cholelithiasis using summary data from large-scale geno...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-025-04162-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849234519498948608 |
|---|---|
| author | Wenhao Tian Zixin Wu Wen Yang Hongyang Wang Qiyu Feng |
| author_facet | Wenhao Tian Zixin Wu Wen Yang Hongyang Wang Qiyu Feng |
| author_sort | Wenhao Tian |
| collection | DOAJ |
| description | Abstract Background Liver injury is associated with cholelithiasis, with changes in liver enzyme levels potentially influencing cholelithiasis risk. This study investigates the shared genetic basis between serum levels of four liver enzymes and cholelithiasis using summary data from large-scale genome-wide association studies (GWAS). Methods We assessed genetic correlation between liver enzymes and cholelithiasis, and performed local genetic correlation analysis to identify shared genomic regions. A cross-trait meta-analysis identified significant SNPs (single nucleotide polymorphisms) shared between the enzymes and cholelithiasis. To explore causal effects, we applied both two-sample Mendelian randomization and multivariable Mendelian randomization. Heritability-based enrichment analysis was employed to identify tissues and cells jointly associated with liver enzymes and cholelithiasis, while summary-data-based Mendelian Randomization (SMR) was utilized to identify shared genes. Results Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) showed relatively stronger genetic correlations with cholelithiasis compared to the other liver enzymes. Shared SNPs were identified among ALT, GGT, alkaline phosphatase (ALP), and cholelithiasis. Mendelian randomization indicated that a tenfold increase in ALT could raise cholelithiasis risk by 203.4%. The liver was identified as the primary tissue linking these enzymes to cholelithiasis, but no shared cell types were implicated. Several candidate genes, such as SPTLC3, may jointly influence liver enzyme levels and cholelithiasis risk. Conclusions Elevated ALT levels may increase cholelithiasis risk. Genetic associations across tissues, genes, and SNPs suggest that liver enzymes could mediate the relationship between liver injury and cholelithiasis risk, providing insights into shared genetic mechanisms with potential implications for future research. |
| format | Article |
| id | doaj-art-0ec8ac8edc164ef18c9b63ca447e6d24 |
| institution | Kabale University |
| issn | 1471-230X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj-art-0ec8ac8edc164ef18c9b63ca447e6d242025-08-20T04:03:07ZengBMCBMC Gastroenterology1471-230X2025-08-0125111810.1186/s12876-025-04162-wInvestigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasisWenhao Tian0Zixin Wu1Wen Yang2Hongyang Wang3Qiyu Feng4Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaCancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaCancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaCancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaCancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAbstract Background Liver injury is associated with cholelithiasis, with changes in liver enzyme levels potentially influencing cholelithiasis risk. This study investigates the shared genetic basis between serum levels of four liver enzymes and cholelithiasis using summary data from large-scale genome-wide association studies (GWAS). Methods We assessed genetic correlation between liver enzymes and cholelithiasis, and performed local genetic correlation analysis to identify shared genomic regions. A cross-trait meta-analysis identified significant SNPs (single nucleotide polymorphisms) shared between the enzymes and cholelithiasis. To explore causal effects, we applied both two-sample Mendelian randomization and multivariable Mendelian randomization. Heritability-based enrichment analysis was employed to identify tissues and cells jointly associated with liver enzymes and cholelithiasis, while summary-data-based Mendelian Randomization (SMR) was utilized to identify shared genes. Results Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) showed relatively stronger genetic correlations with cholelithiasis compared to the other liver enzymes. Shared SNPs were identified among ALT, GGT, alkaline phosphatase (ALP), and cholelithiasis. Mendelian randomization indicated that a tenfold increase in ALT could raise cholelithiasis risk by 203.4%. The liver was identified as the primary tissue linking these enzymes to cholelithiasis, but no shared cell types were implicated. Several candidate genes, such as SPTLC3, may jointly influence liver enzyme levels and cholelithiasis risk. Conclusions Elevated ALT levels may increase cholelithiasis risk. Genetic associations across tissues, genes, and SNPs suggest that liver enzymes could mediate the relationship between liver injury and cholelithiasis risk, providing insights into shared genetic mechanisms with potential implications for future research.https://doi.org/10.1186/s12876-025-04162-wCholelithiasisLiver injuryLiver enzymesGWASShared genetic information |
| spellingShingle | Wenhao Tian Zixin Wu Wen Yang Hongyang Wang Qiyu Feng Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis BMC Gastroenterology Cholelithiasis Liver injury Liver enzymes GWAS Shared genetic information |
| title | Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis |
| title_full | Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis |
| title_fullStr | Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis |
| title_full_unstemmed | Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis |
| title_short | Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis |
| title_sort | investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis |
| topic | Cholelithiasis Liver injury Liver enzymes GWAS Shared genetic information |
| url | https://doi.org/10.1186/s12876-025-04162-w |
| work_keys_str_mv | AT wenhaotian investigatingthesharedgeneticinformationbetweenserumconcentrationlevelsofliverenzymesandcholelithiasis AT zixinwu investigatingthesharedgeneticinformationbetweenserumconcentrationlevelsofliverenzymesandcholelithiasis AT wenyang investigatingthesharedgeneticinformationbetweenserumconcentrationlevelsofliverenzymesandcholelithiasis AT hongyangwang investigatingthesharedgeneticinformationbetweenserumconcentrationlevelsofliverenzymesandcholelithiasis AT qiyufeng investigatingthesharedgeneticinformationbetweenserumconcentrationlevelsofliverenzymesandcholelithiasis |