We tested the 96 markers for association with fracture in 31,016 cases and 102,444 controls from 50 studies with fracture information. This collection included: 5,411 cases and 21,909 controls tested in the BMD GWAS discovery samples, 9,187 cases and 45,057 controls tested by in-silico replication and 16,418 cases and 35,478 controls tested by de-novo genotyping (Figure 1 and Online Methods). In this fracture meta-analysis fourteen loci were significantly associated with any type of fracture at a Bonferroni level (P=5×10−4), of which five included novel BMD loci. None of the markers displayed large estimates of heterogeneity (Table 2, Supplementary Table 6 and Supplementary Fig. 7). Markers at six of these loci reached P<5×10−8 including 18p11.21 (C18orf19), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). The proportion of the overall fracture risk explained by BMD ranged between 0.09 and 0.40 across markers (Supplementary Table 7) and was estimated in a subset of Stage 2 samples (including n=8,594 cases and 23,218 controls) by modeling the BMD SNP effect on fracture risk with and without the inclusion of BMD as covariate.
