Major depressive disorder (MDD) is a notably complex and common illness1. It is often chronic or recurrent and is thus accompanied by considerable morbidity, disability, excess mortality, substantial costs, and heightened risk of suicide2–8. Twin studies attribute approximately 40% of the variation in liability to MDD to additive genetic effects (phenotype heritability, h2)9, and h2 may be greater for recurrent, early-onset, and postpartum MDD10,11. GWA studies of MDD have had notable difficulties in identifying individual associated loci12. For example, there were no significant findings in the initial Psychiatric Genomics Consortium (PGC) MDD mega-analysis (9,240 cases)13 or in the CHARGE meta-analysis of depressive symptoms (N=34,549)14. More recent studies have proven modestly successful. A study of Han Chinese women (5,303 recurrent MDD cases) identified significant loci15, a meta-analysis of depressive symptoms (161,460 individuals) identified two loci16, and an analysis of self-reported major depression identified 15 loci (75,607 cases).
