Correlated phenotypes are also a major issue. Many common diseases and traits (e.g. diabetes, myocardial infarction, obesity, hypertension, metabolic syndrome) are modestly or even highly correlated. Inconsistent susceptibility signals for one of them may reflect consistent associations with another correlated phenotype. Moreover, most common diseases that are assumed to have a complex genetic background are probably a complex mix of different phenotypes in terms of their molecular pathogenesis. Genetic variants may have specific molecular functional effects that cumulatively build a complex clinical phenotype. However, depending on their molecular background, the relative representation of these phenotypes may vary in different people and populations with seemingly the same clinical disease. The case definition of this broad clinical phenotype may not do justice to the underlying molecular complexity. Molecular and clinical phenotypes may exhibit some correlation pattern, but this may vary in different sub-populations depending on the presence of other gene variants. Again, statistical heterogeneity may offer a window to this complexity.
