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. Fields of science medical and health scienceshealth sciencespublic healthmedical and health sciencesclinical medicinerheumatologynatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2012-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator BAR ILAN UNIVERSITY Address Bar ilan university campus 52900 Ramat gan Israel See on map Activity type Higher or Secondary Education Establishments Administrative Contact Estelle Waise (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
