GENOMOS operates in eight workpackages which are coordinated by Dr. André G. Uitterlinden from Erasmus MC in Rotterdam, The Netherlands. The research steering commitee is constituted by Dr. A.G. Uitterlinden, Prof. Dr. Stuart Ralston (Edinbourgh, U.K.) and Prof. Dr. John Ioannidis (Ioannina, Greece).
The research program applies novel tools related to genomics, genetics, bio-informatics, and statistical analysis to establish a collection of osteoporosis risk alleles. The program strategy is focussed on identifying novel risk alleles through several approaches and on testing existing risk alleles, in relation to aspects of osteoporosis (bone mineral density (BMD), bone loss, fracture, gene-nutrient interaction and response to hormone replacement therapy (HRT).
The proposal combines excellent resources to perform such studies with >20.000 subjects by meta-analyses of the data, organisation of meetings, and workshops. Several closely related workpackages are developed by the different participating centers as follows:
- Genotyping of already recognized candidate gene polymorphisms, in population studies involving perimenopausal women and older men and women.
- A large collection of osteoporosis pedigrees will be used to compare linkage- vs. association analysis of osteoporosis risk genes.
- Novel approaches in molecular and statistical analysis of multiple polymorphisms in a single gene (haplotyping) will be used for polymorphism evaluation.
- We will identify polymorphisms of (novel) bone genes, implicated in rare monogenic bone diseases and analyse these in relation to osteoporosis in populations.
- We will seek novel genetic determinants of bone mineral density by using linkage disequilibrium mapping to study loci syntenic to those which regulate BMD in mice. The resulting genes will be further investigated in association studies as described above.
- Meta-analyses of genotype data in all popualtions will be performed to accurately quantify the risk estimates of risk alleles and perform sub-group analysis based on age, gender, ethnicity, and endpoint including fracture, BMD, and bone loss.
- We will study the influence of dietary calcium intake on the effect of osteoporosis risk alleles among different European countries.
- We will determine if there is a genotype-dependent response-to-treatment with hormone replacement therapy in women