Genetics of Rheumatoid Arthritis

The purpose of this protocol is to identify genetic susceptibility loci for rheumatoid arthritis. The Genetics and Genomics Branch of the Intramural Research Program of NIAMS \[now the Inflammatory Diseases Section of the Intramural Research Program of NHGRI\] has joined with several extramural centers to form the North American Rheumatoid Arthritis Consortium (NARAC). The Consortium intends to identify and obtain clinical specimens on a total of 1000 sibling pairs with rheumatoid arthritis; up to 100 sibling pairs will be recruited at the Clinical Center. Samples from parents and other family members will also be obtained, where appropriate. Rheumatoid factors, HLA-DR typings, and hand films will be obtained on all sibling pairs. In addition, DNA will be extracted from peripheral blood or buccal scrapings. The DNA from all 1000 sibling pairs will be typed for a set of approximately 350 genetic markers in order to identify chromosomal regions likely to harbor genes conferring susceptibility to rheumatoid arthritis. For those chromosomal regions that are positive in this initial screen, families will be genotyped for additional markers to define disease-associated haplotypes, and high density single nucleotide polymorphism (SNP) analysis will be conducted to narrow the regions of interest. Candidate genes will be chosen from the narrowed regions of interest, and/or based on functional considerations, and will be screened for mutations in rheumatoid arthritis.