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

EYRE, Steve ; BOWES, John ; AMOS, Christopher I ; PADYUKOV, Leonid ; TOES, Rene E. M ; HUIZINGA, Tom W. J ; WIJMENGA, Cisca ; TRYNKA, Gosia ; FRANKE, Lude ; WESTRA, Harm-Jan ; ALFREDSSON, Lars ; XINLI HU ; DIOGO, Dorothée ; SANDOR, Cynthia ; DE BAKKER, Paul I. W ; DAVILA, Sonia ; CHIEA CHUEN KHOR ; KHAI KOON HENG ; ANDREWS, Robert ; EDKINS, Sarah ; HUNT, Sarah E ; LANGFORD, Cordelia ; SYMMONS, Deborah ; LEE, Annette ; CONCANNON, Pat ; ONENGUT-GUMUSCU, Suna ; RICH, Stephen S ; DELOUKAS, Panos ; GONZALEZ-GAY, Miguela ; RODRIGUEZ-RODRIGUEZ, Luis ; ARLSETIG, Lisbeth ; MARTIN, Javier ; RANTAPÄÄ-DAHLQVIST, Solbritt ; PLENGE, Robert M ; BARTON, Anne ; RAYCHAUDHURI, Soumya ; KLARESKOG, Lars ; GREGERSEN, Peter K ; WORTHINGTON, Jane ; MARTIN, Paul ; ZHERNAKOVA, Alexandra ; STAHL, Eli ; VIATTE, Sebastien ; MCALLISTER, Kate

Nature genetics, 2012-12, Vol.44 (12), p.1336-1340 [Periódico revisado por pares]

New York, NY: Nature Publishing Group

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High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis
Autor: EYRE, Steve ; BOWES, John ; AMOS, Christopher I ; PADYUKOV, Leonid ; TOES, Rene E. M ; HUIZINGA, Tom W. J ; WIJMENGA, Cisca ; TRYNKA, Gosia ; FRANKE, Lude ; WESTRA, Harm-Jan ; ALFREDSSON, Lars ; XINLI HU ; DIOGO, Dorothée ; SANDOR, Cynthia ; DE BAKKER, Paul I. W ; DAVILA, Sonia ; CHIEA CHUEN KHOR ; KHAI KOON HENG ; ANDREWS, Robert ; EDKINS, Sarah ; HUNT, Sarah E ; LANGFORD, Cordelia ; SYMMONS, Deborah ; LEE, Annette ; CONCANNON, Pat ; ONENGUT-GUMUSCU, Suna ; RICH, Stephen S ; DELOUKAS, Panos ; GONZALEZ-GAY, Miguela ; RODRIGUEZ-RODRIGUEZ, Luis ; ARLSETIG, Lisbeth ; MARTIN, Javier ; RANTAPÄÄ-DAHLQVIST, Solbritt ; PLENGE, Robert M ; BARTON, Anne ; RAYCHAUDHURI, Soumya ; KLARESKOG, Lars ; GREGERSEN, Peter K ; WORTHINGTON, Jane ; MARTIN, Paul ; ZHERNAKOVA, Alexandra ; STAHL, Eli ; VIATTE, Sebastien ; MCALLISTER, Kate
Assuntos: Arthritis, Rheumatoid - genetics ; Autoantibodies - blood ; Autoantibodies - genetics ; Autoimmune diseases ; Biological and medical sciences ; Chromosome Mapping - instrumentation ; Chromosome Mapping - methods ; Chromosomes ; Classical genetics, quantitative genetics, hybrids ; Diagnosis ; Disease susceptibility ; Diseases of the osteoarticular system ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic aspects ; Genetic Loci ; Genetic Predisposition to Disease ; Genetics of eukaryotes. Biological and molecular evolution ; Genome-Wide Association Study ; Humans ; Inflammatory joint diseases ; Male ; Medical research ; Medical sciences ; Medicin och hälsovetenskap ; Methods, theories and miscellaneous ; Oligonucleotide Array Sequence Analysis ; Physiological aspects ; Polymorphism, Single Nucleotide ; Rheumatoid arthritis ; Risk factors ; Single nucleotide polymorphisms ; Studies ; Whites - genetics
É parte de: Nature genetics, 2012-12, Vol.44 (12), p.1336-1340
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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These authors contributed equally to this work.
These authors supervised the work equally
Author Contributions J.W, P.K.G, L.K, S.R, R.P and S.E led the study. S.E, J.B, J.W, R.P and S.R wrote the paper. J.B, E.S, S.V, A.Z, P.M, P.I.W.deB, C.I.A, K.Mc, and D.D performed the data and statistical analysis. , A.L, A.B, L.P, R E.M.T, T.W.J.H, C.W, G.T, L.F, H-J.W , L.A, X.H , C.S , S.D, C.C.K, K.K.H, R.A, S.Ed, S.E.H, C.L, D.S, P.C, S.O-G, S.S.R, P.D, M.A.G-G, L.R-R, L.Ä, J.M and S.R-D contributed primarily to the patient ascertainment, sample collection and/or genotyping. All authors reviewed the final manuscript.
Descrição: 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.
Editor: New York, NY: Nature Publishing Group
Idioma: Inglês

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

New York, NY: Nature Publishing Group

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