Epigenomic data facilitate genetic studies for osteoporosis in post-GWAS era

Osteoporosis is a highly prevalent skeletal disease characterized by reduced bone mass and micro-architectural alterations. Similar to breast cancer and stroke, the rate of mortality related to osteoporotic fractures ranges from 15% to 30% (1). Bone mineral density (BMD) is the golden standard in diagnosing osteoporosis and genome-wide association studies (GWASs) have identified many genetic loci for BMD. However, missing heritability is still a problem since current known susceptibility loci can only explain a relatively small fraction of estimated heritability for osteoporosis (2). True association signals may be missed due to the stringent statistical significance thresholds of GWASs. The effectiveness of finding missing heritability by increasing sample size is limited (2).