Age of menarche has been found to be phenotypically and genetically correlated with depression 9, 35, with a causal effect of earlier age at menarche on depressive symptoms also reported 36. The current meta-analysis identified a significant genetic correlation between age of menarche and depression, and nominal evidence of a bi-directional causal effect. The lin-28 homolog b (LIN28B) gene was significant in our meta-analysis and has been associated with age of menarche 37. The biological mechanisms that underlie the association of LIN28B with both age of menarche and depression remain unclear; however, LIN28B has been shown to be involved in regulating cell pluripotency 38 and through its mediation of Lethal-7 miRNA has been implicated in inflammation and immune response 39. The current analysis also identified a novel genetic correlation between age of menopause and depression which may share a similar biological mechanism to that of age of menarche.
