The combined effect of all significant autosomal SNPs on BMD, osteoporosis and any type of fracture was modelled in the PERF study (n=2,836), a prospective study in postmenopausal Danish women aged 55–86 years.17 This study comprises an independent validation setting since it was excluded from the overall meta-analysis for this purpose (see Supplementary Note for details). Risk alleles in the score (i.e., BMD-decreasing alleles) were weighted by their individual effect on BMD and grouped in 5 bins (Supplementary Table 9). The difference in mean FN-BMD between individuals in the highest bin of the risk score (9% of the population; n=244) and those in the middle bin (34% of the population; n=978) was −0.33 SDs (Fig. 3A). This analysis was based on 63 SNPs and explained 5.8% (95%CI [4.0–7.6]) of the total genetic variance in FN-BMD.
