title: Two-dimensional linkage analyses of rheumatoid arthritis.
abstract: 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 x 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 x gene interactions influencing RA using a recently developed two-dimensional linkage method. We found evidence of interacting loci on chromosomes 5, 6, and 18.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, A300 Crabtree Hall, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, USA. nandita@pitt.edu
authors.forename: Nandita
authors.initials: N
authors.lastname: Mukhopadhyay
authors.forename: Indrani
authors.initials: I
authors.lastname: Halder
authors.forename: Samsiddhi
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks