To dissect the genetic overlap observations further, we used uni- and bivariate gaussian mixture modeling, as implemented in MiXeR46, to quantify the actual number of variants that (i) explain 90% of the SNP-heritability of depression, and (ii) overlap between depression and depression-correlated phenotypes. For comparison, we also included two phenotypes showing low genetic correlations with depression (height and Alzheimer’s disease) and one with moderate correlation (epilepsy). 11,750 (SE=310) common variants were estimated to confer liability to depression, suggesting that depression is the most polygenic of the major psychiatric disorders evaluated, showing number of risk variants ranging between 7,000-10,50046,47 (Figure 2, Supplementary Figure S9-1 and Supplementary Table S6A). MiXeR considers all variants irrespective of the direction of correlation (i.e. both variants with same and opposite direction of effects, hereafter collectively referred to as “influencing” variants). The vast majority of variants conferring risk to the other psychiatric disorders investigated were found to influence depression (range 87-99%; Figure 2; Supplementary Table S6A), most pronounced for anxiety, schizophrenia, bipolar disorder and ADHD47 with 95-99% of their risk variants also influencing depression. The other correlated
