Pervasive Sharing of Genetic Effects in Autoimmune Disease

Chris Cotsapas, Benjamin F. Voight, Elizabeth Rossin, Kasper Lage Hansen, Benjamin M. Neale, Chris Wallace, Goncalo R. Abecasis, Jeffrey C. Barrett, Timothy Behrens, Judy Cho, Philip L. De Jager, James T. Elder, Robert R. Graham, Peter Gregersen, Lars Klareskog, Katherine A. Siminovitch, David A. van Heel, Cisca Wijmenga, Jane Worthington, John A. ToddDavid A. Hafler, Stephen S. Rich, Mark J. Daly

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    Abstract

    Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P-CPMA
    Original languageEnglish
    JournalP L o S Genetics
    Volume7
    Issue number8
    ISSN1553-7390
    DOIs
    Publication statusPublished - 2011

    Bibliographical note

    This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License 2.5, which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly cited.

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