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

MacKay, K., Eyre, S., Myerscough, A., Milicic, A., Barton, A., Laval, S., Barrett, J., Lee, D., White, S., John, S., Brown, Matthew A., Bell, J., Silman, A., Ollier, W., Wordsworth, P., & Worthington, J. (2002) Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom. Arthritis and Rheumatism, 46(3), pp. 632-639.

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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, 1 cM from HLA-DRB1) was identified around the major histocompatibility complex (MHC) region on chromosome 6. Suggestive linkage (P < 7.4 × 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 × 10-5). Results of previous genome screens have suggested that 6 of these regions may be involved in RA susceptibility.

Impact and interest:

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ID Code: 87779
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: adult, article, chromosome 10q, chromosome 14q, chromosome 16p, chromosome 21q, chromosome 3p, chromosome 4q, chromosome 6q, chromosome 7p, chromosome Xq, controlled study, DNA sequence, female, gene locus, genetic linkage, genetic susceptibility, genotype, human, linkage analysis, major clinical study, major histocompatibility complex, male, microsatellite marker, polymerase chain reaction, priority journal, rheumatoid arthritis, sibling, United Kingdom, Arthritis, Rheumatoid, Chromosome Mapping, Genetic Predisposition to Disease, Genome, Great Britain, Humans, Linkage (Genetics), Microsatellite Repeats, Nuclear Family, Observer Variation
DOI: 10.1002/art.10147
ISSN: 0004-3591
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 28 Sep 2015 05:20
Last Modified: 28 Sep 2015 05:21

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