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Two-dimensional linkage analyses of rheumatoid arthritis

By Nandita Mukhopadhyay, Indrani Halder, Samsiddhi Bhattacharjee and Daniel E Weeks


Rheumatoid arthritis (RA) is a multifactorial disease with complex genetic etiology, about which little is known. Here, we apply a two-stage procedure in which a quick first-stage analysis was used to narrow down targets for a more thorough and detailed testing for gene × gene interaction. Potentially interesting regions were first identified by testing for major gene effects using non-parametric linkage methods. To select regions of interest, we first tested for linkage to three different RA-related traits one at a time: RA affection status and the quantitative phenotypes rheumatoid factor IgM and anti-cyclic citrullinated peptide levels. These linkage analyses identified regions on chromosomes 3, 5, 6, 8, 16, 18, 19, and 20. We subsequently analyzed the selected regions in a pairwise manner to detect gene × gene interactions influencing RA using a recently developed two-dimensional linkage method. We found evidence of interacting loci on chromosomes 5, 6, and 18

Topics: Proceedings
Publisher: BioMed Central
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Provided by: PubMed Central

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  2. (2006). Analysis for Genetic Epidemiology,
  3. (2005). Characterization of multilocus linkage disequilibrium. Genet Epidemiol
  4. (1993). Chromosome-based method for rapid computer simulation in human genetic linkage analysis. Genet Epidemiol
  5. (2007). CI: Dissecting the heterogeneity of rheumatoid arthritis through linkage analysis of quantitative traits. Arthritis Rheum
  6. (2002). LR: Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet
  7. (2005). Mega2: data-handling for facilitating genetic linkage and association analyses. Bioinformatics
  8. (2001). PK: A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases.
  9. (2006). Recent advances in the genetics of rheumatoid arthritis. Curr Rheumatol Rep
  10. (2006). Two-dimensional genome-scan identifies novel epistatic loci for essential hypertension. Hum Mol Genet
  11. (1995). Two-locus maximum LOD score analysis of a multifactorial trait: joint consideration of