Genome screen for rheumatoid arthritis

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More evidence of shared risk factors with other autoimmune diseases

May 7, 2001

A genome screen for risk factors in rheumatoid arthritis involving the largest collection of US families to date yielded chromosome regions previously implicated in the disease as well as regions implicated in other autoimmune diseases, such as multiple sclerosis and inflammatory bowel disease. The potential hotspots are regions of human chromosomes 1, 4, 12, 16, and 17.

Peter K. Gregersen, of North Shore University Hospital in Manhasset, New York, led the multi-center study involving more than 250 families recruited through the North American Rheumatoid Arthritis Consortium (NARAC). The screens included 379 markers spaced throughout the human genome. Statistical analyses using the markers and DNA from pairs of siblings were carried out to determine chromosome regions that may contain genes of interest.

Structure of Families in the North American Rheumatoid Arthritis Consortium (NARAC) Collection
	Number of Families
Parents Available	Overall (n = 257)	With Two Affected Sibs (n = 231)	With Three Affected Sibs (n = 240	With Four Affected Sibs (n = 2)
Both	36	32	4	0
One	92	84	8	0
None	129	115^a	12	2
^a From one of these 115 families, five unaffected siblings were available for analysis. Otherwise, information from unaffected siblings was not used. Source: The American Journal of Human Genetics

Published data connect rheumatoid arthritis to human leukocyte antigen (HLA)-linked genes, which reside in a complex on chromosome 6. "This study was undertaken specifically to identify genes outside of the HLA region," the researchers write in a recent issue of The American Journal of Human Genetics. "Given the increasing evidence for familial aggregation and genetic overlap among different autoimmune diseases, we also looked for evidence of common mapping results with other large linkage-mapping studies of autoimmune diseases."

Five of the non-HLA regions reported in the study have been implicated in at least one other autoimmune disease, including multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus, and ankylosing spondylitis.

The researchers conclude: "Genes in the HLA complex play a major role in rheumatoid arthritis susceptibility, but several other regions also contribute significantly to overall genetic risk."

. . .

Jawaheer, D. et al. A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. Am J Hum Genet 68, 927-936 (April 2001).

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