the difference between the number of loci with effects in the same direction and the number with effects in opposite directions. This, however, is an underestimate because loci with weak effects may have estimated effects in opposite directions in the two stages. To allow for this possibility, we fitted the distribution of z scores as a mixture of a standard normal distribution (representing SNPs with no effect) and a normal distribution with unknown mean and variance, using an expectation-maximization algorithm58. The total contribution to heritability was then computed from the posterior estimates. To allow for the potential effect of residual population stratification, we conducted an additional analysis in which the null distribution was assumed to have variance of 1.2, based on the estimated inflation from the non-BCAC SNPs, but the estimates were essentially identical.
