With the advent of genome-wide association studies (GWAS), the number of genetic discoveries has increased dramatically for all complex diseases, and such is the case for osteoporosis. To date, at least 70 bone mineral density (BMD) loci have shown robust association with BMD, while several efforts on other osteoporosis traits are underway. Here, we have focused on a subset of these loci and reviewed the candidate genes which are likely (yet not unequivocally) to be underlying the GWAS signals. Many of the identified variants map in the vicinity of genes of unknown function (representing cutting-edge new biology), while several other factors cluster within critical biological pathways relevant for bone biology, like Wnt signaling, OPG-RANK-RANKL mesenchymal cell differentiation and Indian hedgehog pathways. Thus far, these genes identified by GWAS incorporate variants, which together explain 8%-10% of the variation in BMD, thus limiting its application for meaningful clinical risk prediction. On the other hand, the translation of these GWAS discoveries into therapeutic applications for the treatment of osteoporosis seems an upcoming reality.

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Keywords Bone biology, Bone mineral density, Genes, Genome-wide association study, Loci, Osteoporosis
Persistent URL dx.doi.org/10.1016/B978-0-12-804182-6.00022-8, hdl.handle.net/1765/104437
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Rivadeneira Ramirez, F, & Uitterlinden, A.G. (2017). Osteoporosis Genes Identified by Genome-Wide Association Studies. In Genetics of Bone Biology and Skeletal Disease: Second Edition (pp. 377–395). doi:10.1016/B978-0-12-804182-6.00022-8