Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom

MacKay, Kirsten, Eyre, Stephen, Myerscough, Anne, Milicic, Anita, Barton, Anne, Laval, Steven, Barrett, Jenny, Lee, Dorothea, White, Sarah, John, Sally, Brown, Matthew A., Bell, John, Silman, Alan, Ollier, William, Wordsworth, Paul and Worthington, Jane (2002) Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom. Arthritis and Rheumatism, 46 3: 632-639. doi:10.1002/art.10147


Author MacKay, Kirsten
Eyre, Stephen
Myerscough, Anne
Milicic, Anita
Barton, Anne
Laval, Steven
Barrett, Jenny
Lee, Dorothea
White, Sarah
John, Sally
Brown, Matthew A.
Bell, John
Silman, Alan
Ollier, William
Wordsworth, Paul
Worthington, Jane
Title Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
1529-0131
Publication date 2002-03
Sub-type Article (original research)
DOI 10.1002/art.10147
Volume 46
Issue 3
Start page 632
End page 639
Total pages 8
Place of publication Hoboken. N.J., United Kingdom
Publisher John Wiley & Sons
Language eng
Subject 0604 Genetics
110322 Rheumatology and Arthritis
Formatted abstract
Objective.
To undertake a systematic wholegenome screen to identify regions exhibiting genetic linkage to rheumatoid arthritis (RA).

Methods.
Two hundred fifty-two RA-affected sibling pairs from 182 UK families were genotyped using 365 highly informative microsatellite markers. Microsatellite genotyping was performed using fluorescent polymerase chain reaction primers and semiautomated DNA sequencing technology. Linkage analysis was undertaken using MAPMAKER/SIBS for single-point and multipoint analysis.

Results.
Significant linkage (maximum logarithm of odds score 4.7 [P = 0.000003] at marker D6S276, I cM from HLA-DRB1) was identified around the major histocompatibility complex (MHC) region on chromosome 6. Suggestive linkage (P < 7.4 X 10(-4)) was identified on chromosome 6q by single- and multipoint analysis. Ten other sites of nominal linkage (P < 0.05) were identified on chromosomes 3p, 4q, 7p, 2 regions of 10q, 2 regions of 14q, 16p, 21q, and Xq by single-point analysis and on 3 sites (1q, 14q, and 14q) by multipoint analysis.

Conclusion.

Linkage to the MHC region was confirmed. Eleven non-HLA regions demonstrated evidence of suggestive or nominal linkage, but none reached the genome-wide threshold for significant linkage (P = 2.2 X 10(-5)). Results of previous genome screens have suggested that 6 of these regions may be involved in RA susceptibility.
Keyword Rheumatology
Complex Traits
Identification
Nationwide
Strategies
Diseases
Screen
Twins
Hla
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Erratum: Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom (vol 46,pg 632, 2002)

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
 
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Created: Fri, 25 Jan 2008, 15:34:00 EST