GS:SFHS is a family and population-based study consisting of 23,690 participants recruited via general medical practices across Scotland. The recruitment protocol and sample characteristics are described in detail elsewhere11,12. Briefly, participants were over 18 years old, and not ascertained on the basis of having any particular disorder. A diagnosis of depression (MDD) was made using the structured clinical interview for DSM-IV disorders (SCID)15. Participants who answered yes to either of the two screening questions were invited to continue the interview, which provided information on the presence or absence of a lifetime history of MDD, age of onset and number of depressive episodes. Participants who answered no to both screening questions or who completed the SCID but did not meet the criteria for depression were assigned control status. Case definition was further refined through NHS data linkage. Controls with a history of antidepressants or who had been referred to a secondary psychiatric care centre (n = 1 072) were excluded, as were cases who had received a previous diagnosis of schizophrenia or bipolar disorder (n = 47). This resulted in 2603
