Pervasive Sharing of Genetic Effects in Autoimmune Disease

Publication: Research - peer-reviewJournal article – Annual report year: 2011

  • Author: Cotsapas, Chris

    Massachusetts General Hospital

  • Author: Voight, Benjamin F.

    Massachusetts General Hospital

  • Author: Rossin, Elizabeth

    Massachusetts General Hospital

  • Author: Hansen, Kasper Lage

    Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark

  • Author: Neale, Benjamin M.

    Massachusetts General Hospital

  • Author: Wallace, Chris

    University of Cambridge

  • Author: Abecasis, Goncalo R.

    University of Michigan

  • Author: Barrett, Jeffrey C.

    Wellcome Trust Sanger Institute, Cambridge

  • Author: Behrens, Timothy

    Genentech, South San Francisco

  • Author: Cho, Judy

    Yale University

  • Author: De Jager, Philip L.

    Harvard Medical School

  • Author: Elder, James T.

    University of Michigan

  • Author: Graham, Robert R.

    Genentech, South San Francisco

  • Author: Gregersen, Peter

    Feinstein Institute for Medical Research

  • Author: Klareskog, Lars

    Karolinska Institute

  • Author: Siminovitch, Katherine A.

    Mount Sinai Hospital, Toronto

  • Author: van Heel, David A.

    The London School of Medicine and Dentistry

  • Author: Wijmenga, Cisca

    University of Groningen

  • Author: Worthington, Jane

    University of Manchester

  • Author: Todd, John A.

    University of Cambridge

  • Author: Hafler, David A.

    Yale University

  • Author: Rich, Stephen S.

    University of Virginia

  • Author: Daly, Mark J.

    Massachusetts General Hospital

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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
Publication date2011
Volume7
Issue8
ISSN1553-7390
DOIs
StatePublished

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.

CitationsWeb of Science® Times Cited: 106
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