Abstract

MARTINEZ-GIL, Núria et al. Genome-wide association studies (GWAS) vs functional validation: the challenge of the post-GWAS era. Rev Osteoporos Metab Miner [online]. 2023, vol.15, n.1, pp.29-39.  Epub May 29, 2023. ISSN 2173-2345.  https://dx.doi.org/10.20960/revosteoporosmetabminer.000008.

Over the past few years, efforts have been made to determine the variants and genes that may be important to determine bone mineral density (BMD) that, at the same time, are involved in several bone diseases. To achieve this, the approach that has been the most successful of all has been genome-wide association studies (GWAS). In particular, in research on bone biology over 50 different large GWAS or GWAS metanalyses have been published identifying a total of 500 genetic loci associated with different bone parameters such as BMD, bone resistance, and risk of fracture. Although the discovery of associated variants is an essential aspect, the functional validation of such variants is equally important to elucidate their effect, as well as the causal correlation they have with genetic disease. Since it is a much more time consuming and tedious aspect it has become the new challenge of this post-GWAS era. Among the genes that have already been studied several Wnt signaling pathway genes have been included, among them, the SOST gene that plays a crucial role both determining the BMD of the population and monogenic diseases with elevated bone mass giving rise to a new therapy against osteoporosis. In this review we’ll be collecting the main GWAS associated with bone phenotypes, as well as some functional validations undertaken to analyze the associations found in them.

Keywords : Genome-wide association studies; Functional validation; Bone mineral density; Bone diseases.

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