Little attention has been given so far to the extent of the effect of heterogeneity on genetic association findings in common complex diseases. Testing the impact of heterogeneity on GWAS findings requires extensive knowledge of the pathophysiology and genetic architecture of the common trait under study. This assumption makes psychiatric disorders unsuitable for such analysis. On the other hand, another common disease such as diabetes mellitus (DM) is suitable for testing the impact of heterogeneity. The two types of DM were distinguished only in the late 1930s [20], each characterized by distinct pathophysiology [21] and genetic architecture. If a diagnosis of DM was based on high blood glucose alone, DM type 1 (T1D) cases could not be differentiated from DM type 2 (T2D) cases. The state of DM classification prior to 1930 may well approximate the state of knowledge about psychiatric disorders in the beginning of the 21st century.
