Two independent alleles at 6q23 associated with risk of rheumatoid arthritis
This is an issue edsumm for 27. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association an...
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| Vydané v: | Nature genetics Ročník 39; číslo 12; s. 1477 - 1482 |
|---|---|
| Hlavní autori: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
New York
Nature Publishing Group US
01.12.2007
Nature Publishing Group |
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| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
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| Abstract | This is an issue edsumm for 27. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence.
To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study
1
. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, ∼150 kb from
TNFAIP3
and
OLIG3
) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (
P
= 10
−3
, GWA scan;
P
< 10
−6
, replication;
P
= 10
−9
, combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220;
P
= 5 × 10
−6
in WTCCC)
2
. We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. |
|---|---|
| AbstractList | To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, 6150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10 super(-3), GWA scan; P < 10 super(-6), replication; P = 10 super(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 10 super(-6) in WTCCC). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study super(1). After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, [math]150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10 super(-3), GWA scan; P < 10 super(-6), replication; P = 10 super(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 [math] 10 super(-6) in WTCCC) super(2). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. This is an issue edsumm for 27. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study 1 . After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, ∼150 kb from TNFAIP3 and OLIG3 ) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples ( P = 10 −3 , GWA scan; P < 10 −6 , replication; P = 10 −9 , combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 × 10 −6 in WTCCC) 2 . We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, approximately 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 x 10(-6) in WTCCC). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23.To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, approximately 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 x 10(-6) in WTCCC). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study1. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, ∼150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10−3, GWA scan; P < 10−6, replication; P = 10−9, combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 × 10−6 in WTCCC)2. We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, approximately 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 x 10(-6) in WTCCC). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. |
| Audience | Academic |
| Author | Klareskog, Lars Roubenoff, Ronenn Gregersen, Peter K Parker, Alexander N Karlson, Elizabeth W Purcell, Shaun Padyukov, Leonid Remmers, Elaine F Maller, Julian de Bakker, Paul I W Coblyn, Jonathan Seldin, Michael F Healy, Claire Glass, Roberta Lee, David M Graham, Robert R DeFelice, Matt Weinblatt, Michael E Parkin, Melissa Izmailova, Elena Barry, Rachel Maher, Nancy Cotsapas, Chris Lee, Annette T Pe'er, Itsik Winslow, Wendy Gabriel, Stacey B Daly, Mark J Plenge, Robert M Hafler, David A Price, Alkes L Burtt, Noel P Blumenstiel, Brendan Shadick, Nancy A Davies, Leela Alfredsson, Lars Neale, Benjamin M Altshuler, David |
| AuthorAffiliation | 2 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA 3 Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA 6 Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK 8 Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA 1 Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA 10 Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA 4 Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massa |
| AuthorAffiliation_xml | – name: 10 Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA – name: 7 Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, USA – name: 3 Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA – name: 4 Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA – name: 2 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA – name: 11 The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, USA – name: 13 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden – name: 8 Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA – name: 9 Rowe Program in Genetics, University of California at Davis, Davis, California 95616, USA – name: 5 Department of Computer Science, Columbia University, New York, New York 10027, USA – name: 6 Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK – name: 12 Rheumatology Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden – name: 1 Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA |
| Author_xml | – sequence: 1 givenname: Robert M surname: Plenge fullname: Plenge, Robert M email: rplenge@partners.org organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School – sequence: 2 givenname: Chris surname: Cotsapas fullname: Cotsapas, Chris organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School – sequence: 3 givenname: Leela surname: Davies fullname: Davies, Leela organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 4 givenname: Alkes L surname: Price fullname: Price, Alkes L organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School – sequence: 5 givenname: Paul I W surname: de Bakker fullname: de Bakker, Paul I W organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School – sequence: 6 givenname: Julian surname: Maller fullname: Maller, Julian organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School – sequence: 7 givenname: Itsik surname: Pe'er fullname: Pe'er, Itsik organization: Department of Computer Science, Columbia University – sequence: 8 givenname: Noel P surname: Burtt fullname: Burtt, Noel P organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 9 givenname: Brendan surname: Blumenstiel fullname: Blumenstiel, Brendan organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 10 givenname: Matt surname: DeFelice fullname: DeFelice, Matt organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 11 givenname: Melissa surname: Parkin fullname: Parkin, Melissa organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 12 givenname: Rachel surname: Barry fullname: Barry, Rachel organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 13 givenname: Wendy surname: Winslow fullname: Winslow, Wendy organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 14 givenname: Claire surname: Healy fullname: Healy, Claire organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology – sequence: 15 givenname: Robert R surname: Graham fullname: Graham, Robert R organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School – sequence: 16 givenname: Benjamin M surname: Neale fullname: Neale, Benjamin M organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London – sequence: 17 givenname: Elena surname: Izmailova fullname: Izmailova, Elena organization: Millennium Pharmaceuticals – sequence: 18 givenname: Ronenn surname: Roubenoff fullname: Roubenoff, Ronenn organization: Millennium Pharmaceuticals – sequence: 19 givenname: Alexander N surname: Parker fullname: Parker, Alexander N organization: Millennium Pharmaceuticals – sequence: 20 givenname: Roberta surname: Glass fullname: Glass, Roberta organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School – sequence: 21 givenname: Elizabeth W surname: Karlson fullname: Karlson, Elizabeth W organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School – sequence: 22 givenname: Nancy surname: Maher fullname: Maher, Nancy organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School – sequence: 23 givenname: David A surname: Hafler fullname: Hafler, David A organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School – sequence: 24 givenname: David M surname: Lee fullname: Lee, David M organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School – sequence: 25 givenname: Michael F surname: Seldin fullname: Seldin, Michael F organization: Rowe Program in Genetics, University of California at Davis – sequence: 26 givenname: Elaine F surname: Remmers fullname: Remmers, Elaine F organization: Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health – sequence: 27 givenname: Annette T surname: Lee fullname: Lee, Annette T organization: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System – sequence: 28 givenname: Leonid surname: Padyukov fullname: Padyukov, Leonid organization: Department of Medicine, Rheumatology Unit, Karolinska Institutet at Karolinska University Hospital Solna – sequence: 29 givenname: Lars surname: Alfredsson fullname: Alfredsson, Lars organization: Institute of Environmental Medicine, Karolinska Institutet – sequence: 30 givenname: Jonathan surname: Coblyn fullname: Coblyn, Jonathan organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School – sequence: 31 givenname: Michael E surname: Weinblatt fullname: Weinblatt, 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Shore-Long Island Jewish Health System – sequence: 36 givenname: Nancy A surname: Shadick fullname: Shadick, Nancy A organization: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School – sequence: 37 givenname: Mark J surname: Daly fullname: Daly, Mark J organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School – sequence: 38 givenname: David surname: Altshuler fullname: Altshuler, David organization: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19924985$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/17982456$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:116280216$$DView record from Swedish Publication Index (Karolinska Institutet) |
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| Snippet | This is an issue edsumm for 27. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence.
To identify susceptibility alleles... To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried... |
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| SubjectTerms | Agriculture Alleles Animal Genetics and Genomics Arthritis, Rheumatoid - genetics Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Case-Control Studies Chromosomes, Human, Pair 6 Classical genetics, quantitative genetics, hybrids Diagnosis Diseases of the osteoarticular system Female Fundamental and applied biological sciences. Psychology Gene Function Gene loci Genetic aspects Genetic Predisposition to Disease Genetics of eukaryotes. Biological and molecular evolution Genome, Human Genotype & phenotype Haplotypes Health risk assessment Human Genetics Humans Inflammatory joint diseases letter Male Medical research Medical sciences Methods, theories and miscellaneous Physiological aspects Polymorphism, Single Nucleotide Rheumatoid arthritis Risk factors Single nucleotide polymorphisms |
| Title | Two independent alleles at 6q23 associated with risk of rheumatoid arthritis |
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