ABSTRACT

Background & aims:

‍Adiposity, type 2 diabetes, alcohol and coffee consumption and smoking have been examined in relation to diverticular disease in observational studies. We conducted a Mendelian randomization study to assess the causality of these associations.

Methods:

‍Independent genetic instruments associated with the studied exposures at genome-wide significance were obtained from published genome-wide association studies. Summary-level data for the exposure-associated SNPs with diverticular disease were available in the FinnGen consortium (10 978 cases and 149 001 non-cases) and the UK Biobank study (12 662 cases and 348 532 non-cases).

Results:

‍Higher genetically predicted body mass index and genetic liability to type 2 diabetes and smoking initiation were associated with an increased risk of diverticular disease in meta-analyses of results from the two studies. The combined odds ratio (OR) of diverticular disease was 1.23 (95% confidence interval (CI), 1.14, 1.33; p<0.001) for one standard deviation (∼4.8 kg/m2) increase in body mass index, 1.04 (95% CI, 1.01, 1.07; p=0.007) for one-unit increase in log-transformed odds ratio of type 2 diabetes, and 1.21 (95% CI, 1.12, 1.30; p<0.001) for one standard deviation increase in prevalence of smoking initiation. Coffee consumption was not associated with diverticular disease, whereas the association for alcohol consumption largely differed between the two studies.

Conclusions:

‍This study strengthens the causal associations of higher body mass index, type 2 diabetes and smoking with an increased risk of diverticular disease. Coffee consumption is not associated with diverticular disease. Whether alcohol consumption affects the risk of diverticular disease need further investigation.