Complex traits, like BMD, may be not only the results of cumulatively additive effects of individual genetic factors, but also the results of gene interaction via biological pathways/networks [28]. Under WGCNA, we found ASB16-AS1 co-expressed with more than forty genes which were proven to be associated with BMD by previous studies. The result thus suggested that ASB16-AS1 may play an important role in bone biology. In the ASB16-AS1 centered network, gene CTNNB1 encodes β-catenin protein which can aggregate and move into the nucleus and then can active wnt/β-catenin signaling pathway. The target gene of β-catenin protein, RUNX2, is active to promote osteoblast proliferation and differentiation [51–53]. Interestingly, these genes which mainly play roles in osteoblasts, were found to be co-expressed with ASB16-AS1 in PBMs which are precursors of osteoclasts [33]. The reason why these genes express in PBMs was worth of further exploration. TNFSF11 was negatively correlated with ASB16-AS1. RANKL encoded by TNFSF11 is a key factor for osteoclast differentiation and activation [54]. Taken together, we predicted that ASB16-AS1 may play important roles in osteoblast and osteoclast proliferation and differentiation.
