Title: Investigating the shared genetic information between serum concentration levels of liver
enzymes and cholelithiasis
Version: 2 Date: 30 May 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: “Investigating the Shared Genetic Information Between Serum Concentration Levels of
Liver Enzymes and Cholelithiasis”
Thank you for the opportunity to review this well-executed and ambitious study. Your
manuscript tackles a highly relevant and biologically intriguing topic by leveraging genome-
wide association study (GWAS) data to investigate the genetic correlation, shared loci, and
potential causal links between serum liver enzyme levels and cholelithiasis. The combination of
cross-trait meta-analysis, Mendelian randomization, and functional enrichment adds significant
depth to the analysis.
The strength of your work lies in its integration of multiple statistical and genomic
methodologies, including LD score regression, LOGODetect, MTAG, and both univariable and
multivariable Mendelian randomization approaches. The careful consideration of confounders
such as BMI and cholesterol, along with the use of publicly available and well-curated datasets,
increases the robustness of your findings. The conclusion that elevated ALT may increase
cholelithiasis risk and that certain genes like SPTLC3 may mediate this relationship is both
plausible and clinically relevant.
In summary, this is a high-quality manuscript that uses a sophisticated and well-justified
methodology to address a biologically and clinically important question. please add a clear
conclusion section. yet I recommend on accepting the manuscript.
Sincerely,
Title: Investigating the shared genetic information between serum concentration levels of liver
enzymes and cholelithiasis
Version: 2 Date: 30 May 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: “Investigating the Shared Genetic Information Between Serum Concentration Levels of
Liver Enzymes and Cholelithiasis”
Thank you for the opportunity to review this well-executed and ambitious study. Your
manuscript tackles a highly relevant and biologically intriguing topic by leveraging genome-
wide association study (GWAS) data to investigate the genetic correlation, shared loci, and
potential causal links between serum liver enzyme levels and cholelithiasis. The combination of
cross-trait meta-analysis, Mendelian randomization, and functional enrichment adds significant
depth to the analysis.
The strength of your work lies in its integration of multiple statistical and genomic
methodologies, including LD score regression, LOGODetect, MTAG, and both univariable and
multivariable Mendelian randomization approaches. The careful consideration of confounders
such as BMI and cholesterol, along with the use of publicly available and well-curated datasets,
increases the robustness of your findings. The conclusion that elevated ALT may increase
cholelithiasis risk and that certain genes like SPTLC3 may mediate this relationship is both
plausible and clinically relevant.
In summary, this is a high-quality manuscript that uses a sophisticated and well-justified
methodology to address a biologically and clinically important question. please add a clear
conclusion section. yet I recommend on accepting the manuscript.
Sincerely,
Please review this paper.
user
Title: Investigating the shared genetic information between serum concentration levels of liver
enzymes and cholelithiasis
Version: 2 Date: 30 May 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: “Investigating the Shared Genetic Information Between Serum Concentration Levels of
Liver Enzymes and Cholelithiasis”
Thank you for the opportunity to review this well-executed and ambitious study. Your
manuscript tackles a highly relevant and biologically intriguing topic by leveraging genome-
wide association study (GWAS) data to investigate the genetic correlation, shared loci, and
potential causal links between serum liver enzyme levels and cholelithiasis. The combination of
cross-trait meta-analysis, Mendelian randomization, and functional enrichment adds significant
depth to the analysis.
The strength of your work lies in its integration of multiple statistical and genomic
methodologies, including LD score regression, LOGODetect, MTAG, and both univariable and
multivariable Mendelian randomization approaches. The careful consideration of confounders
such as BMI and cholesterol, along with the use of publicly available and well-curated datasets,
increases the robustness of your findings. The conclusion that elevated ALT may increase
cholelithiasis risk and that certain genes like SPTLC3 may mediate this relationship is both
plausible and clinically relevant.
In summary, this is a high-quality manuscript that uses a sophisticated and well-justified
methodology to address a biologically and clinically important question. please add a clear
conclusion section. yet I recommend on accepting the manuscript.
Sincerely,
assistant