Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

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Title: Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis
Authors: Hamshere, Marian L.
Segurado, Ricardo
Moskvina, Valentina
Nikolov, Ivan
Glaser, Beate
Holmans, Peter
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Date: 18-Dec-2007
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.
Type of material: Journal Article
Publisher: BioMed Central
Copyright (published version): 2007 Hamshere et al; licensee BioMed Central Ltd.
Keywords: Rheumatoid factorHigh risk alleleNorthern American Rheumatoid ConsortiumOrder subset analysisRheumatoid arthritis family
Language: en
Status of Item: Peer reviewed
Appears in Collections:Public Health, Physiotherapy and Sports Science Research Collection

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