Title: The associations between modifiable risk factors and constipation: A comprehensive
Mendelian randomization study
Version: 0 Date: 13 Dec 2023
Reviewer:  Danilo Consalvo
Reviewer's report:
The study is very interesting because it focuses on Mendelian randomization.
In Mendelian randomization is very important to respect the three core instrumental variable
assumptions: relevance, independence and exclusion restriction assumptions.
Recent scientific literature highlights its effectiveness in researching the effectiveness of drugs
on some pathologies and of some risk factors on some other pathologies.
In this study the instrumental variables considered (37) are not so interesting in understanding
risk factors of constipation.
The results was a significant association between genetically predicted gastroesophageal reflux
disease and an increased risk of constipation and a potential association between severe
depression and the use of aspirin with an increased risk of constipation.
It is not clear methodologically what the hypothesis is: is constipation the cause of
gastroesophageal reflux or vice versa? Or is it only a correlation?
I suggest the search for further instrumental variables such as taking opioid drugs, therapy for
Parkinson's, hypothyroidism, genetically based amyloidosis.
The discussion could be modified by starting from the evidence from RCTs and then comparing
this with the evidence from Mendelian randomization.
Title: The associations between modifiable risk factors and constipation: A comprehensive
Mendelian randomization study
Version: 0 Date: 13 Dec 2023
Reviewer:  Danilo Consalvo
Reviewer's report:
The study is very interesting because it focuses on Mendelian randomization.
In Mendelian randomization is very important to respect the three core instrumental variable
assumptions: relevance, independence and exclusion restriction assumptions.
Recent scientific literature highlights its effectiveness in researching the effectiveness of drugs
on some pathologies and of some risk factors on some other pathologies.
In this study the instrumental variables considered (37) are not so interesting in understanding
risk factors of constipation.
The results was a significant association between genetically predicted gastroesophageal reflux
disease and an increased risk of constipation and a potential association between severe
depression and the use of aspirin with an increased risk of constipation.
It is not clear methodologically what the hypothesis is: is constipation the cause of
gastroesophageal reflux or vice versa? Or is it only a correlation?
I suggest the search for further instrumental variables such as taking opioid drugs, therapy for
Parkinson's, hypothyroidism, genetically based amyloidosis.
The discussion could be modified by starting from the evidence from RCTs and then comparing
this with the evidence from Mendelian randomization.
Please review this paper.
user
Title: The associations between modifiable risk factors and constipation: A comprehensive
Mendelian randomization study
Version: 0 Date: 13 Dec 2023
Reviewer:  Danilo Consalvo
Reviewer's report:
The study is very interesting because it focuses on Mendelian randomization.
In Mendelian randomization is very important to respect the three core instrumental variable
assumptions: relevance, independence and exclusion restriction assumptions.
Recent scientific literature highlights its effectiveness in researching the effectiveness of drugs
on some pathologies and of some risk factors on some other pathologies.
In this study the instrumental variables considered (37) are not so interesting in understanding
risk factors of constipation.
The results was a significant association between genetically predicted gastroesophageal reflux
disease and an increased risk of constipation and a potential association between severe
depression and the use of aspirin with an increased risk of constipation.
It is not clear methodologically what the hypothesis is: is constipation the cause of
gastroesophageal reflux or vice versa? Or is it only a correlation?
I suggest the search for further instrumental variables such as taking opioid drugs, therapy for
Parkinson's, hypothyroidism, genetically based amyloidosis.
The discussion could be modified by starting from the evidence from RCTs and then comparing
this with the evidence from Mendelian randomization.
assistant