The sensitivity of different analytical methods to detect disease susceptibility genes in rheumatoid arthritis sibling pair families

Angela Marlow, Sally John, Ali Hajeer, William E R Ollier, Alan J. Silman, Jane Worthington

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Our aim was to compare the sensitivity of 4 analytical methods to detect linkage to a known disease susceptibility locus, HLA-DRB1, in 100 rheumatoid arthritis sibling pair families with incomplete parental genotype information. Genotypes for the HLA-DRB1 and HLA-A loci were analyzed using (1) identity-by-descent (IBD), considering inheritance of maternal and paternal alleles separately; (2) maximum likelihood score-IBD (MLS-IBD), which infers missing parental genotypes; (3) identity-by-state (IBS), which does not require parental genotypes; and (4) transmission disequilibrium test (TDT), which uses affected offspring with a heterozygous parent. Due to the small number of informative meoisis for HLA-DRB1, the IBD analysis was not significant for linkage (p = 0.014). HLA-A was more informative (p = 0.0002). The MLS-IBD method for HLA-DRB1 (p = 0.00004) and HLA-A (p ≤ 0.00001) was significant. Using IBS both loci gave highly significant evidence of linkage, (p
    Original languageEnglish
    Pages (from-to)208-211
    Number of pages3
    JournalJournal of Rheumatology
    Volume24
    Issue number1
    Publication statusPublished - Jan 1997

    Keywords

    • disease susceptibility
    • epidemiology
    • genes
    • rheumatoid arthritis

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