"Osteoporosis is a common, age-related disease with a strong genetic component. With increasing age of the population, Europe and industrialised countries across the globe are facing a substantial increase in osteoporotic fractures, which account for considerable disease-burden and costs. Early identification and treatment of subjects at risk can help preventing this, and genetic susceptibility alleles are the most promising risk factors in this respect. Large-scale prospective meta-analysis of individual gene polymorphisms in the EU-funded GENOMOS consortium was shown successful in identifying the expected subtle effects of gene polymorphisms which predispose to osteoporosis. The recent development of powerful genome-wide genotyping technology now allows to identify -hypothesis free- strong and common genetic risk factors for complex diseases by Genome Wide Association (GWA) analysis. The AIM of the proposal is to identify osteoporosis susceptibility alleles by meta-analysis of GWA data obtained from a large collection of osteoporosis genetics cohorts in Europe and outside (n=46.000). Prospective meta-analysis of GENOMOS, a large consortium of genetic studies on osteoporosis (n=80.000), is used to assess generalizability of genetic effects and develop sufficient power to quantify even small, but clinically important risks. The improvement in clinical risk-assessment for osteoporosis by adding the diagnostic panel of osteoporosis risk-alleles identified in this project, will be quantified in prospective studies including genetic and classical risk factors."