Large-scale Linkage Analysis of 1302 Affected Relative Pairs with Rheumatoid Arthritis

Overview

Journal BMC Proc

Publisher Biomed Central

Specialty Biology

Date 2008 May 10

PMID 18466440

Citations 1

Authors

Marian L Hamshere

Ricardo Segurado

Valentina Moskvina

Ivan Nikolov

Beate Glaser

Peter A Holmans

Affiliations

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Abstract

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates.

Citing Articles

Combining linkage data sets for meta-analysis and mega-analysis: the GAW15 rheumatoid arthritis data set.

Segurado R, Hamshere M, Glaser B, Nikolov I, Moskvina V, Holmans P BMC Proc. 2008; 1 Suppl 1:S104.

PMID: 18466444 PMC: 2367583. DOI: 10.1186/1753-6561-1-s1-s104.

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