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The IRF5-TNPO3 asso...
The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
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- Kottyan, Leah C. (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA,Liver Centre, Toronto Western Hospital, Toronto, ON, Canada.
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- Zoller, Erin E. (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology
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- Bene, Jessica (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology
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visa fler...
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- Lu, Xiaoming (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology
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- Kelly, Jennifer A. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Rupert, Andrew M. (författare)
- Division of Biomedical Informatics, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, USA.,Department of Biostatistical Sciences and Center for Public Health Genomics
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- Lessard, Christopher J. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Pathology
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- Vaughn, Samuel E. (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology
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- Marion, Miranda (författare)
- Karolinska Institutet,NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK.,Division of Rheumatology, University of Minnesota Medical School, Minneapolis, MN, USA.,Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.,University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, USA.,University of Washington and Seattle Childrens Hospital, Seattle, WA, USA.,Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
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- Weirauch, Matthew T. (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA Division of Biomedical Informatics, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, USA.
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- Namjou, Bahram (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology
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- Adler, Adam (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Valley Bone and Joint Clinic, Grand Forks, ND, USA.,Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.,Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA, USA.
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- Rasmussen, Astrid (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Glenn, Stuart (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Montgomery, Courtney G. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.,Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
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- Hirschfield, Gideon M. (författare)
- NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK.
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- Xie, Gang (författare)
- Mount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, ON, Canada.
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- Coltescu, Catalina (författare)
- Liver Centre, Toronto Western Hospital, Toronto, ON, Canada.
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- Amos, Chris (författare)
- Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
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- Li, He (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Pathology and.
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- Ice, John A. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Nath, Swapan K. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Mariette, Xavier (författare)
- Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, INSERM U1012, Le Kremlin Bicêtre, France.
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- Bowman, Simon (författare)
- Rheumatology Department, University Hospital Birmingham, Birmingham, UK.
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- Rischmueller, Maureen (författare)
- The Queen Elizabeth Hospital, Adelaide, Australia.
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- Lester, Sue (författare)
- The Queen Elizabeth Hospital, Adelaide, Australia The University of Adelaide, Adelaide, Australia.
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- Brun, Johan G. (författare)
- Institute of Internal Medicine, University of Bergen, Bergen, Norway Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
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- Gøransson, Lasse G. (författare)
- Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
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- Harboe, Erna (författare)
- Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
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- Omdal, Roald (författare)
- Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
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- Cunninghame-Graham, Deborah S. (författare)
- Department of Medical and Molecular Genetics, Kings College London, London, UK.
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- Vyse, Tim (författare)
- Department of Medical and Molecular Genetics, Kings College London, London, UK.
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- Miceli-Richard, Corinne (författare)
- Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, INSERM U1012, Le Kremlin Bicêtre, France.
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- Brennan, Michael T. (författare)
- Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA.
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- Lessard, James A. (författare)
- Valley Bone and Joint Clinic, Grand Forks, ND, USA.
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- Wahren-Herlenius, Marie (författare)
- Department of Medicine, Karolinska Institute, Stockholm, Sweden.
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- Kvarnström, Marika (författare)
- Department of Medicine, Karolinska Institute, Stockholm, Sweden.
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- Illei, Gabor G. (författare)
- National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
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- Witte, Torsten (författare)
- Hannover Medical School, Hanover, Germany.
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- Jonsson, Roland (författare)
- Department of Rheumatology, Haukeland University Hospital, Bergen, Norway Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway.
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- Eriksson, Per, 1958- (författare)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Avdelningen för inflammation och infektion,Region Östergötland, Reumatologiska kliniken i Östergötland,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Nordmark, Gunnel (författare)
- Uppsala universitet,Reumatologi,Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.
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- Ng, Wan-Fai (författare)
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
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- Anaya, Juan-Manuel (författare)
- Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia.
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- Rhodus, Nelson N. (författare)
- Department of Oral Surgery, University of Minnesota School of Dentistry, Minneapolis, MN, USA.
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- Segal, Barbara M. (författare)
- Division of Rheumatology, University of Minnesota Medical School, Minneapolis, MN, USA.
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- Merrill, Joan T. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- James, Judith A. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
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- Guthridge, Joel M. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Hal Scofield, R (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Division of Veterans Affairs Medical Center, Oklahoma City, OK, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
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- Alarcon-Riquelme, Marta (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA de Genómica e Investigación Oncológica (GENYO), Pfizer-Universidad de Granada-Junta de Andalucia, Granada, Spain.
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- Bae, Sang-Cheol (författare)
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
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- Boackle, Susan A. (författare)
- Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.
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- Criswell, Lindsey A. (författare)
- Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA, USA.
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- Gilkeson, Gary (författare)
- Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
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- Kamen, Diane L (författare)
- Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
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- Jacob, Chaim O. (författare)
- Divison of Gastrointestinal and Liver Diseases, Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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- Kimberly, Robert (författare)
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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- Brown, Elizabeth (författare)
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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- Edberg, Jeffrey (författare)
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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- Alarcón, Graciela S. (författare)
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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- Reveille, John D. (författare)
- Division of Rheumatology and Clinical Immunogenetics, The Univeristy of Texas Health Science Center at Houston, Houston, TX, USA.
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- Vilá, Luis M. (författare)
- University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, USA.
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- Petri, Michelle (författare)
- Division of Rheumatology, Johns Hopkins, Baltimore, MD, USA.
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- Ramsey-Goldman, Rosalind (författare)
- Division of Rheumatology, Northwestern University, Chicago, IL, USA.
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- Freedman, Barry I. (författare)
- Wake Forest School of Medicine, Winston-Salem, NC, USA.
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- Niewold, Timothy (författare)
- Division of Rheumatology and Immunology, Mayo Clinic, Rochester, MN, USA.
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- Stevens, Anne M. (författare)
- University of Washington and Seattle Childrens Hospital, Seattle, WA, USA.
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- Tsao, Betty P. (författare)
- David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
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- Ying, Jun (författare)
- MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
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- Mayes, Maureen D. (författare)
- MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
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- Gorlova, Olga Y. (författare)
- MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
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- Wakeland, Ward (författare)
- University of Texas Southwestern Medical School, Dallas, TX, USA.
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- Radstake, Timothy (författare)
- Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
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- Martin, Ezequiel (författare)
- Instituto de Parasitología y Biomedicina López Neyra Avda, Granada, Spain and.
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- Martin, Javier (författare)
- Instituto de Parasitología y Biomedicina López Neyra Avda, Granada, Spain and.
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- Siminovitch, Katherine (författare)
- Mount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, ON, Canada Department of Medicine, University of Toronto, Toronto, ON, Canada.
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- Moser Sivils, Kathy L. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Gaffney, Patrick M. (författare)
- Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
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- Langefeld, Carl D. (författare)
- Department of Biostatistical Sciences and Center for Public Health Genomics and.
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- Harley, John B. (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
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- Kaufman, Kenneth M. (författare)
- Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
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Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA Liver Centre, Toronto Western Hospital, Toronto, ON, Canada (creator_code:org_t)
- 2014-09-08
- 2015
- Engelska.
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
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Kottyan, Leah C.
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Zoller, Erin E.
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Bene, Jessica
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Lu, Xiaoming
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Rupert, Andrew M ...
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Adler, Adam
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Glenn, Stuart
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Montgomery, Cour ...
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Hirschfield, Gid ...
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Xie, Gang
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Coltescu, Catali ...
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Amos, Chris
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Li, He
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Ice, John A.
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Nath, Swapan K.
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Mariette, Xavier
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Bowman, Simon
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Rischmueller, Ma ...
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Lester, Sue
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Brun, Johan G.
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Gøransson, Lasse ...
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Harboe, Erna
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Omdal, Roald
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Cunninghame-Grah ...
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Vyse, Tim
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Miceli-Richard, ...
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Brennan, Michael ...
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Lessard, James A ...
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Wahren-Herlenius ...
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Kvarnström, Mari ...
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Illei, Gabor G.
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Witte, Torsten
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Jonsson, Roland
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Eriksson, Per, 1 ...
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Nordmark, Gunnel
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Ng, Wan-Fai
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Anaya, Juan-Manu ...
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Rhodus, Nelson N ...
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Segal, Barbara M ...
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Merrill, Joan T.
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James, Judith A.
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Guthridge, Joel ...
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Hal Scofield, R
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Alarcon-Riquelme ...
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Bae, Sang-Cheol
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Boackle, Susan A ...
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Criswell, Lindse ...
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Gilkeson, Gary
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Kamen, Diane L
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Jacob, Chaim O.
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Kimberly, Robert
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Brown, Elizabeth
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Edberg, Jeffrey
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Alarcón, Graciel ...
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Reveille, John D ...
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Vilá, Luis M.
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Petri, Michelle
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Ramsey-Goldman, ...
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Freedman, Barry ...
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Niewold, Timothy
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Stevens, Anne M.
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Tsao, Betty P.
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Ying, Jun
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Mayes, Maureen D ...
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Gorlova, Olga Y.
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Wakeland, Ward
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Radstake, Timoth ...
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Martin, Ezequiel
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Martin, Javier
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Siminovitch, Kat ...
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Moser Sivils, Ka ...
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Gaffney, Patrick ...
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Langefeld, Carl ...
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Harley, John B.
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Kaufman, Kenneth ...
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