Prior epidemiological studies associated MDD with many other diseases and traits. Due to limitations inherent to observational studies, understanding whether a phenotypic correlation is potentially causal or if it results from reverse causation or confounding is generally difficult. Genetic studies now offer complementary strategies to assess whether a phenotypic association between MDD and a risk factor or a comorbidity is mirrored by a non-zero rg (common variant genetic correlation) and, for some of these, evaluate the potential causality of the association given that exposure to genetic risk factors begins at conception.
