One of the unanswered questions about obesity is how it correlates with a myriad of diseases such as heart failure, coronary artery disease, type 2 diabetes, non-alcoholic fatty liver disease, osteoarthritis, and various cancers. One possibility is certainly that the risk factors for these diseases are also risk factors for obesity; the risk factors for these diseases affect the risk of the diseases independent (completely or partially) of their risk of obesity. In our paper, we took one risk factor for obesity or the polygenic risk score for BMI  and we showed that it is also a risk factor for all of the diseases that are comorbid with obesity. Furthermore, we showed that when we adjust for BMI the risk of the comorbid diseases disappears either completely or partially. We believe it is likely that in the cases where there is a remnant of the risk after adjustment for BMI, it could be explained by the fact that we adjust simply for one measurement of BMI rather than the lifetime BMI. Hence, our conclusion is that the risk of the comorbid diseases caused by polygenic risk score for BMI is mediated through BMI and not through some separate effect on their risk. We believe that this raises questions about how the current treatments for obesity, the medicines as well as bariatric surgery, diminish the risk of the comorbid diseases.  Is it simply by affecting weightloss or through direct effect on the risk of the comorbid diseases? The results of our study could be looked upon as support for the first possibility.

https://vimeo.com/1023255678/5728d8badb