Mendelian randomization for causal inference of the relationship between obesity and 28-day survival following septic shock

Septic shock is a leading cause of death in intensive care units. Septic shock occurs when a body-wide infection leads to low blood pressure, and ultimately organ failure. Some recent studies suggest that overweight and obese patients have a better chance of survival following septic shock than normal or underweight patients. In this project we apply Mendelian randomization to assess whether the observed obesity effect on 28-day survival following septic shock is causal or more likely due to unmeasured confounding variables. Mendelian randomization is an instrumental variables approach that uses genetic markers as instruments. Under modelling assumptions, unconfounded estimates of the obesity effect can be obtained by fitting a model for 28-day survival that includes a residual obesity term. Data for the project comes from the Vasopressin and Septic Shock Trial (VASST). Our analysis suggests that the observed obesity effect on survival following septic shock is not causal.