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High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

Abstract

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

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  • Authors+Show Affiliations

    ,

    Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

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    Source

    Nature genetics 44:12 2012 Dec pg 1336-40

    MeSH

    Arthritis, Rheumatoid
    Autoantibodies
    Chromosome Mapping
    European Continental Ancestry Group
    Female
    Genetic Loci
    Genetic Predisposition to Disease
    Genome-Wide Association Study
    Humans
    Male
    Oligonucleotide Array Sequence Analysis
    Polymorphism, Single Nucleotide

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23143596

    Citation

    Eyre, Steve, et al. "High-density Genetic Mapping Identifies New Susceptibility Loci for Rheumatoid Arthritis." Nature Genetics, vol. 44, no. 12, 2012, pp. 1336-40.
    Eyre S, Bowes J, Diogo D, et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet. 2012;44(12):1336-40.
    Eyre, S., Bowes, J., Diogo, D., Lee, A., Barton, A., Martin, P., ... Worthington, J. (2012). High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nature Genetics, 44(12), pp. 1336-40. doi:10.1038/ng.2462.
    Eyre S, et al. High-density Genetic Mapping Identifies New Susceptibility Loci for Rheumatoid Arthritis. Nat Genet. 2012;44(12):1336-40. PubMed PMID: 23143596.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. AU - Eyre,Steve, AU - Bowes,John, AU - Diogo,Dorothée, AU - Lee,Annette, AU - Barton,Anne, AU - Martin,Paul, AU - Zhernakova,Alexandra, AU - Stahl,Eli, AU - Viatte,Sebastien, AU - McAllister,Kate, AU - Amos,Christopher I, AU - Padyukov,Leonid, AU - Toes,Rene E M, AU - Huizinga,Tom W J, AU - Wijmenga,Cisca, AU - Trynka,Gosia, AU - Franke,Lude, AU - Westra,Harm-Jan, AU - Alfredsson,Lars, AU - Hu,Xinli, AU - Sandor,Cynthia, AU - de Bakker,Paul I W, AU - Davila,Sonia, AU - Khor,Chiea Chuen, AU - Heng,Khai Koon, AU - Andrews,Robert, AU - Edkins,Sarah, AU - Hunt,Sarah E, AU - Langford,Cordelia, AU - Symmons,Deborah, AU - ,, AU - ,, AU - Concannon,Pat, AU - Onengut-Gumuscu,Suna, AU - Rich,Stephen S, AU - Deloukas,Panos, AU - Gonzalez-Gay,Miguel A, AU - Rodriguez-Rodriguez,Luis, AU - Ärlsetig,Lisbeth, AU - Martin,Javier, AU - Rantapää-Dahlqvist,Solbritt, AU - Plenge,Robert M, AU - Raychaudhuri,Soumya, AU - Klareskog,Lars, AU - Gregersen,Peter K, AU - Worthington,Jane, Y1 - 2012/11/11/ PY - 2012/05/10/received PY - 2012/10/10/accepted PY - 2012/11/13/entrez PY - 2012/11/13/pubmed PY - 2013/2/14/medline SP - 1336 EP - 40 JF - Nature genetics JO - Nat. Genet. VL - 44 IS - 12 N2 - Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. SN - 1546-1718 UR - https://www.unboundmedicine.com/medline/citation/23143596/High_density_genetic_mapping_identifies_new_susceptibility_loci_for_rheumatoid_arthritis_ L2 - http://dx.doi.org/10.1038/ng.2462 DB - PRIME DP - Unbound Medicine ER -