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A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2001 Apr; Vol. 68 (4), pp. 927-36. Date of Electronic Publication: 2001 Mar 09. - Publication Year :
- 2001
-
Abstract
- Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using 379 microsatellite markers. A nonparametric analysis using SIBPAL confirmed linkage of the HLA locus to RA (P < .00005), with lambdaHLA = 1.79. However, the analysis also revealed a number of non-HLA loci on chromosomes 1 (D1S235), 4 (D4S1647), 12 (D12S373), 16 (D16S403), and 17 (D17S1301), with evidence for linkage at a significance level of P<.005. Analysis of X-linked markers using the MLOD method from ASPEX also suggests linkage to the telomeric marker DXS6807. Stratifying the families into white or seropositive subgroups revealed some additional markers that showed improvement in significance over the full data set. Several of the regions that showed evidence for nominal significance (P < .05) in our data set had previously been implicated in RA (D16S516 and D17S1301) or in other diseases of an autoimmune nature, including systemic lupus erythematosus (D1S235), inflammatory bowel disease (D4S1647, D5S1462, and D16S516), multiple sclerosis (D12S1052), and ankylosing spondylitis (D16S516). Therefore, genes in the HLA complex play a major role in RA susceptibility, but several other regions also contribute significantly to overall genetic risk.
- Subjects :
- Alleles
Chromosome Mapping
Chromosomes, Human genetics
Female
HLA Antigens genetics
Humans
Lod Score
Male
Matched-Pair Analysis
Microsatellite Repeats genetics
Middle Aged
Nuclear Family
Software
Statistics, Nonparametric
United States
White People genetics
X Chromosome genetics
Arthritis, Rheumatoid genetics
Autoimmune Diseases genetics
Genetic Predisposition to Disease genetics
Genetic Testing
Genome, Human
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9297
- Volume :
- 68
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 11254450
- Full Text :
- https://doi.org/10.1086/319518