Bethesda, Maryland 20892

  • Rheumatoid Arthritis


This study attempts to identify the genes responsible for rheumatoid arthritis (RA), or inflammation of the joints. It is known that genes play an important role in RA, but their number and significance have not been determined. RA tends to run in families. This study will examine the DNA (hereditary material) of patients with RA and their family members to try to determine which chromosomes(s) contain the genes responsible for the disease. Patients with rheumatoid arthritis and their family members may be eligible for this study. Participants with RA who have a brother or sister with RA will undergo the following procedures: - Review of their medical records - Medical history - Examination of the joints - Hand X-rays - Blood tests Participants who 1) do not have RA but who have a relative with the disease, or 2) have RA and a relative other than a brother or sister who has the disease will provide a blood sample or a buccal (cheek) cell sample. Cheek cells are obtained by swishing a small amount of mouthwash in the mouth or by lightly bushing the inside of the cheek with a swab or brush. The samples will be tested for rheumatoid factor, DNA studies, and HLA type (a blood type found on white blood cells). Certain HLA types have been associated with an increased risk or severity of RA.

Study summary:

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.


- INCLUSION CRITERIA: SIBLING PAIR: A diagnosis of rheumatoid arthritis in both sibs by the 1987 ACR criteria. Definite bony erosions in at least one affected sibling. Age of disease onset greater than 18 years and less than 60 years in at least one sibling. Neither sibling has psoriasis, inflammatory bowel disease, or systemic lupus erythematosus. BLOOD RELATIVES OF AFFECTED SIBLING PAIRS: Age greater than 18 years. Where possible, all other affected siblings will be invited to participate. Where possible, both parents of affected siblings will be invited to participate. Other relatives, both affected and unaffected, may be invited to participate if, in the opinion of the investigators, samples from these individuals would contribute important genetic information. Two cases in which this might happen are: a) extended families in which there are several affected individuals, where conventional linkage analysis might be applied; b) affected sibling pairs for which parents are unavailable, where additional siblings will provide information on parental alleles not transmitted to the affected siblings. EXCLUSION CRITERIA FOR AFFECTED SIBLINGS: Psoriasis, inflammatory bowel disease, systemic lupus erythematosus. Inability to provide infomed consent. The sole criterion for exclusion of adult blood relatives of affected sibling pairs would be inability to provide informed consent.

Study is Available At:

Original ID:




Secondary ID:


Study Acronym:

Brief Title:

Genetics of Rheumatoid Arthritis

Official Title:

Genetics of Rheumatoid Arthritis: The North American Rheumatoid Arthritis Consortium

Overall Status:


Study Phase:




Minimum Age:

18 Years

Maximum Age:


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institutes of Health Clinical Center (CC)

Oversight Authority:

United States: Federal Government

Reasons Why Stopped:

Study Type:


Study Design:

Number of Arms:


Number of Groups:


Total Enrollment:


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Overall Contact Information

Official Name:Daniel L Kastner, M.D.
Principal Investigator
National Human Genome Research Institute (NHGRI)

Study Dates

Start Date:July 7, 1998
Completion Date:June 20, 2014
Verification Date:June 20, 2014
Last Changed Date:October 5, 2017
First Received Date:November 3, 1999

Study Outcomes

There are no available Study Outcomes

Study Interventions

There are no available Study Interventions

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Human Genome Research Institute (NHGRI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Harris ED Jr. Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990 May 3;322(18):1277-89. Review. Erratum in: N Engl J Med 1990 Oct 4;323(14):996.
Reference Type:Reference
Citation:Lawrence RC, Hochberg MC, Kelsey JL, McDuffie FC, Medsger TA Jr, Felts WR, Shulman LE. Estimates of the prevalence of selected arthritic and musculoskeletal diseases in the United States. J Rheumatol. 1989 Apr;16(4):427-41.
Reference Type:Reference
Citation:Stastny P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med. 1978 Apr 20;298(16):869-71.

Data Source:

Date Processed: July 27, 2021

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