Genetic analysis reveals etiologic heterogeneity in major depression

Results from genome-wide association studies have led to the view that the genetic architecture of psychiatric disorders arises primarily from multiple variants each contributing a small effect to disease risk. Using a highly... [ view full abstract ]

Results from genome-wide association studies have led to the view that the genetic architecture of psychiatric disorders arises primarily from multiple variants each contributing a small effect to disease risk. Using a highly selected cohort of 4,785 women with recurrent major depression (MD) and 4,814 screened controls, we show that the 26% of cases who report major adverse life events only partly share genetic risk factors with the 74% who did not. We report three loci whose effects are only significantly associated with MD in those reporting no history of adversity. Significant interaction occurs between self-reported adversity and genotype at all three loci. Findings are consistent with etiologic heterogeneity within MD. Our results indicate that the relationship between environmental and genetic susceptibility varies across loci, and have implications for the molecular dissection of MD and other complex traits.