Cases were recruited from clinical settings and through media and internet announcements and advertisements. After giving written informed consent, participants were interviewed by phone or in person using the Diagnostic Interview for Genetic Studies20 version 3 (http://nimhgenetics.org). Two independent expert reviewers achieved consensus ratings of DSM-IV mood and comorbid disorder diagnoses and associated course of illness variables, based on the DIGS, a narrative summary, and available treatment records and/or informant reports from the Family Interview for Genetic Studies (FIGS). Eligible probands had an MDD diagnosis, two or more episodes (or one episode lasting at least three years), onset before age 31, at least one sibling or parent with recurrent MDD with onset before age 41, MDD independent of substance dependence (i.e., no lifetime dependence, prior to dependence, or after at least two years of remission from dependence), no diagnosis of bipolar or schizoaffective disorder or schizophrenia, and no suspected bipolar-I disorder in a parent or sibling.10 In GenRED I, at least one affected sibling was directly interviewed. In GenRED II, MDD in a parent or sibling was documented by FIGS
