Although there is a considerable corpus of research on the epidemiology and biological correlates of MDD, little is known for certain about its etiology. An important etiological clue may be the familial tendency of MDD and its heritability of 31-42% (16). This clue led to a number of genomewide linkage studies (Supplemental Methods) and studies of >100 theoretical or positional candidate genes. As for the use of these study designs with other biomedical disorders, their application to MDD has not been as successful as had been hoped.
