GWAS FOR FRACTURES

Genome-Wide Search for Pleiotropic Genes Governing Vertebral Fractures

Coordinatore	BAR ILAN UNIVERSITY    more  Organization address address: BAR ILAN UNIVERSITY CAMPUS city: RAMAT GAN postcode: 52900 contact info Titolo: Ms. Nome: Estelle Cognome: Waise Email: send email Telefono: 97235317439 Fax: 97236353277
Nazionalità Coordinatore	Israel [IL]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-CIG
Funding Scheme	MC-CIG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-08-01   -   2016-07-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	BAR ILAN UNIVERSITY  Organization address address: BAR ILAN UNIVERSITY CAMPUS city: RAMAT GAN postcode: 52900 contact info Titolo: Ms. Nome: Estelle Cognome: Waise Email: send email Telefono: 97235317439 Fax: 97236353277	IL (RAMAT GAN)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Vertebral fractures (VertFrx) are the most common osteoporotic fractures, with a prevalence of 30%-50% in people over age 50; these fractures are accompanied by severe consequences. Despite the enormous personal and public health impact of VertFrx, the underlying biologic mechanisms remain largely unknown. VertFrx are heritable, however, their genetics have not been systematically studied. We hypothesize that VertFrx, as well as their risk factors, - bone mineral density (BMD), bone geometry, and muscle mass, - are governed by shared genetic polymorphisms, which will be discovered by a multi-trait genome-wide association study (GWAS). During a 4-year period, we will explore the following Specific Aims: 1) to obtain data from five musculoskeletal phenotypes: (1) VertFrx; (2) vertebral volumetric BMD (vBMD); (3) vertebral cross-sectional area (CSA); (4) paraspinal muscle area; (5) paraspinal muscle attenuation (density) at the level of the third lumbar vertebra (L3) using existing CT scans in adult men and women of European descent. 2) to identify genetic regions shared among VertFrx and vertebral vBMD, bone CSA, and paraspinal muscle area and density at the level of L3, by meta-analysis of GWAS results from several collaborating cohorts. 3) to replicate the association of potentially-pleiotropic polymorphisms identified in aim 2, using the the VertFrx phenotype in a large European consortium (GEFOS/GENOMOS). 4) to validate the expression of top novel genes in primary bone and muscle cells, and osteoblast-like, osteocyte-like, and myoblasts-like cell lines, and assess functional polymorphisms using several bone and muscle cell lines, and whole tissue samples. The outcome of this project will be a list of replicated pleiotropic polymorphisms with evidence of functional significance. An additional goal of this project is to help integrating an expert in the genetic epidemiology of aging-related diseases, as a faculty member in the newly-formed Faculty of Medicine.'