We used Mendelian randomization (MR) to assess whether causal effects exist between depression and a number of other traits and disorders. MR uses genetic variants as a proxy for environmental exposures, assuming that: i) the genetic variants are associated with the exposure; ii) the genetic variants are independent of confounders in the exposure-outcome association; iii) the genetic variants are associated with the outcome only via their effect on the exposure, i.e. there is no horizontal pleiotropy whereby the variants affect both exposure and outcome independently. Individual genetic variants may be weak instruments for assessing causality, particularly if they have only small effect sizes. Using multiple genetic variants can increase the strength of the instrument, but also increases the risk of violating the MR assumptions.
