Objective
Rheumatoid Arthritis is a common chronic autoimmune disease that affects approximately 1% of the adult population worldwide.Although its causes are largely unknown, it is clear that there is a considerable heritable component. In 2007, three genome-wide association studies (GWAS) as well as candidate gene approaches successfully increased the number of RA gene loci from two to five. More recently, a meta-analysis of these GWAS has been completed (Nature Genetics, in press). The most significant finding outside of the known RA risk loci was of a common polymorphism near the CD40 gene (odds ratio = 0.87 p = 5.1 x 10-9). While this represents a true disease gene, several questions remain to be answered to fully comprehend the role of CD40 mutations in RA pathogenesis. While this study provides direct evidence that CD40 is critical in RA pathogenesis, at least three crucial questions remain: 1) what is the exact common causal mutation? 2) Are there rare mutations that contribute to disease not accounted for in the genome-wide studies as they are designed to identify common mutations? 3) What is the biological relevance of both types of CD40 mutations? My proposed research will address these three critical questions by applying next generation genetic technologies (e.g. high-throughput Solexa sequencing) in large RA case-control collections available in the Plenge laboratory at Harvard Medical School (Outgoing Host Institute), together with functional immunology available in the Huizinga laboratory at Leiden University Medical Center (Return Host Institute). To achieve my goals, genetic and immunological resources will be combined to identify, validate and functionally characterise both common and rare functional mutations involved in the establishment of RA. This comprehensive approach will generate insight into a pathway relevant to disease development.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine rheumatology
- medical and health sciences basic medicine immunology autoimmune diseases
- natural sciences biological sciences genetics mutation
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-IOF-2008
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
2333 ZA Leiden
Netherlands
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