Common and rare variants of WNT16, DKK1 and SOST and their relationship with bone mineral density

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  • dc.contributor.author Martínez-Gil, Núria
  • dc.contributor.author Roca Ayats, Neus
  • dc.contributor.author Monistrol-Mula, Anna
  • dc.contributor.author García-Giralt, Natalia
  • dc.contributor.author Diez-Perez, Adolfo
  • dc.contributor.author Nogués Solan, Francesc Xavier
  • dc.contributor.author Mellibovsky, Leonardo
  • dc.contributor.author Grinberg, Daniel
  • dc.contributor.author Balcells, Susana
  • dc.date.accessioned 2019-07-16T07:30:22Z
  • dc.date.available 2019-07-16T07:30:22Z
  • dc.date.issued 2018
  • dc.description.abstract Numerous GWAS and candidate gene studies have highlighted the role of the Wnt pathway in bone biology. Our objective has been to study in detail the allelic architecture of three Wnt pathway genes: WNT16, DKK1 and SOST, in the context of osteoporosis. We have resequenced the coding and some regulatory regions of these three genes in two groups with extreme bone mineral density (BMD) (n = ∼50, each) from the BARCOS cohort. No interesting novel variants were identified. Thirteen predicted functional variants have been genotyped in the full cohort (n = 1490), and for ten of them (with MAF > 0.01), the association with BMD has been studied. We have found six variants nominally associated with BMD, of which 2 WNT16 variants predicted to be eQTLs for FAM3C (rs55710688, in the Kozak sequence and rs142005327, within a putative enhancer) withstood multiple-testing correction. In addition, two rare variants in functional regions (rs190011371 in WNT16b 3'UTR and rs570754792 in the SOST TATA box) were found only present in three women each, all with BMD below the mean of the cohort. Our results reinforce the higher importance of regulatory versus coding variants in these Wnt pathway genes and open new ways for functional studies of the relevant variants.
  • dc.description.sponsorship We thank M. Pineda, N. Stender, R. Urreizti and M. Cozar for relevant technical assistance. Funds for the study include grants SAF2014-56562-R and SAF2016-75948-R (Spanish MINECO), and CIBERER (U720). NMG is a recipient of a FI predoctoral fellowship from Generalitat de Catalunya; NRA is a recipient of a FPU predoctoral fellowship from the Spanish Ministerio de Educación Cultura y Deporte.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Martínez-Gil N, Roca-Ayats N, Monistrol-Mula A, García-Giralt N, Díez-Pérez A, Nogués X. et al. Common and rare variants of WNT16, DKK1 and SOST and their relationship with bone mineral density. Sci Rep. 2018 Jul 19;8(1):10951. DOI: 10.1038/s41598-018-29242-8
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-018-29242-8
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/42001
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-56562-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75948-R
  • dc.rights Copyright © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Ossos -- Fisiologia
  • dc.subject.other Osteoporosi
  • dc.subject.other Genètica
  • dc.title Common and rare variants of WNT16, DKK1 and SOST and their relationship with bone mineral density
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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