Invited Abstracts IS 1 The EN 1 Story : The gains from imputation and whole genome sequencing

Using what was the world’s largest whole genome sequencing based study, we identified novel non-coding genetic variants with large effects on BMD (n=53,236) and fracture (n=508,253). We identified a novel locus in the human genome with low frequency non-coding variants near EN1. The effect sizes of these genetic variants were fourfold larger than the mean of previously reported common genetic variants and they also decreased the risk of osteoporotic fracture. We explored the causal role of EN1 by generating an En1cre/flox mouse model and observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover.