Our study has limitations. The identified SNPs are probably not the causal variants; it is more likely that these markers are in LD with the underlying causal variants. Additional analyses on potential functional SNPs identified in this study will be required to determine if they are causal to these relationships with BMD. Moreover, the causal genes underlying the GWAS signals may be different from the candidate genes we describe, considering that our understanding of their role in bone biology is limited. Further exploration of these loci with more detailed sequencing, gene expression, and translational studies will be required. Such studies can also disentangle the diverse types of complex relationships we currently cannot distinguish in the BMD loci with secondary signals, i.e., if these are the result of true allelic heterogeneity or if they are driven by a second gene in the same region.32 Similarly, despite our large sample size, power limitations still play a role for detecting additional associations with smaller effect sizes and/or arising from rarer variants. Finally, given the different levels of data availability and the difficulties for
