We tested the association between the 96 SNPs and BMD and fracture risk in each in-silico and de-novo “Stage 2” study separately as described for the “Stage 1” studies. We subsequently meta-analyzed effects and standard errors from the “Stage 2” studies, followed by a meta-analysis of the summary statistics of both “Stage 1” and “Stage 2” using the inverse-variance method in METAL. At this replication stage, where more than 30 studies were synthesized, we chose to first assess the underlying heterogeneity considering both the Cochran’s Q statistic and the I2 metric. If the heterogeneity was not significant fixed effects models were applied. If the Cochrane Q P-value<0.0005 and the I2 was > 50% we used the more conservative random effects models.
