Pervasive sharing of genetic effects in autoimmune disease

Chris Cotsapas, Benjamin F. Voight, Elizabeth Rossin, Kasper Lage, Benjamin M. Neale, Chris Wallace, Gonçalo R. AbecasisGonç, 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

    Research output: Contribution to journalArticlepeer-review

    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
    Article numbere1002254
    JournalPL o S Genetics
    Volume7
    Issue number8
    DOIs
    Publication statusPublished - Aug 2011

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