The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.

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Kottyan, Leah C.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. (författare)

The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.

Artikel/kapitelEngelska2015

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2014-09-08
Oxford University Press (OUP),2015
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LIBRIS-ID:oai:DiVA.org:liu-113873
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-113873URI
https://doi.org/10.1093/hmg/ddu455DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-234553URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:130808618URI

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Språk:engelska
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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.

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Biuppslag (personer, institutioner, konferenser, titlar ...)

Zoller, Erin E.Division of Rheumatology, Center for Autoimmune Genomics and Etiology (författare)
Bene, JessicaDivision of Rheumatology, Center for Autoimmune Genomics and Etiology (författare)
Lu, XiaomingDivision of Rheumatology, Center for Autoimmune Genomics and Etiology (författare)
Kelly, Jennifer A.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Rupert, Andrew M.Division of Biomedical Informatics, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, USA.,Department of Biostatistical Sciences and Center for Public Health Genomics (författare)
Lessard, Christopher J.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Pathology (författare)
Vaughn, Samuel E.Division of Rheumatology, Center for Autoimmune Genomics and Etiology (författare)
Marion, MirandaKarolinska 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. (författare)
Weirauch, Matthew T.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. (författare)
Namjou, BahramDivision of Rheumatology, Center for Autoimmune Genomics and Etiology (författare)
Adler, AdamArthritis 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. (författare)
Rasmussen, AstridArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Glenn, StuartArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Montgomery, Courtney G.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. (författare)
Hirschfield, Gideon M.NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK. (författare)
Xie, GangMount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, ON, Canada. (författare)
Coltescu, CatalinaLiver Centre, Toronto Western Hospital, Toronto, ON, Canada. (författare)
Amos, ChrisDepartment of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA. (författare)
Li, HeArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Pathology and. (författare)
Ice, John A.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Nath, Swapan K.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Mariette, XavierDepartment of Rheumatology, Hôpitaux Universitaires Paris-Sud, INSERM U1012, Le Kremlin Bicêtre, France. (författare)
Bowman, SimonRheumatology Department, University Hospital Birmingham, Birmingham, UK. (författare)
Rischmueller, MaureenThe Queen Elizabeth Hospital, Adelaide, Australia. (författare)
Lester, SueThe Queen Elizabeth Hospital, Adelaide, Australia The University of Adelaide, Adelaide, Australia. (författare)
Brun, Johan G.Institute of Internal Medicine, University of Bergen, Bergen, Norway Department of Rheumatology, Haukeland University Hospital, Bergen, Norway. (författare)
Gøransson, Lasse G.Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway. (författare)
Harboe, ErnaClinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway. (författare)
Omdal, RoaldClinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway. (författare)
Cunninghame-Graham, Deborah S.Department of Medical and Molecular Genetics, Kings College London, London, UK. (författare)
Vyse, TimDepartment of Medical and Molecular Genetics, Kings College London, London, UK. (författare)
Miceli-Richard, CorinneDepartment of Rheumatology, Hôpitaux Universitaires Paris-Sud, INSERM U1012, Le Kremlin Bicêtre, France. (författare)
Brennan, Michael T.Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. (författare)
Lessard, James A.Valley Bone and Joint Clinic, Grand Forks, ND, USA. (författare)
Wahren-Herlenius, MarieDepartment of Medicine, Karolinska Institute, Stockholm, Sweden. (författare)
Kvarnström, MarikaDepartment of Medicine, Karolinska Institute, Stockholm, Sweden. (författare)
Illei, Gabor G.National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA. (författare)
Witte, TorstenHannover Medical School, Hanover, Germany. (författare)
Jonsson, RolandDepartment of Rheumatology, Haukeland University Hospital, Bergen, Norway Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway. (författare)
Eriksson, Per,1958-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(Swepub:liu)perer22 (författare)
Nordmark, GunnelUppsala universitet,Reumatologi,Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.(Swepub:uu)gunnnord (författare)
Ng, Wan-FaiInstitute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. (författare)
Anaya, Juan-ManuelCenter for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia. (författare)
Rhodus, Nelson N.Department of Oral Surgery, University of Minnesota School of Dentistry, Minneapolis, MN, USA. (författare)
Segal, Barbara M.Division of Rheumatology, University of Minnesota Medical School, Minneapolis, MN, USA. (författare)
Merrill, Joan T.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
James, Judith A.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. (författare)
Guthridge, Joel M.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Hal Scofield, RArthritis 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. (författare)
Alarcon-Riquelme, MartaArthritis 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. (författare)
Bae, Sang-CheolDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea. (författare)
Boackle, Susan A.Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA. (författare)
Criswell, Lindsey A.Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA, USA. (författare)
Gilkeson, GaryDivision of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA. (författare)
Kamen, Diane LDivision of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA. (författare)
Jacob, Chaim O.Divison of Gastrointestinal and Liver Diseases, Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. (författare)
Kimberly, RobertDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. (författare)
Brown, ElizabethDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. (författare)
Edberg, JeffreyDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. (författare)
Alarcón, Graciela S.Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. (författare)
Reveille, John D.Division of Rheumatology and Clinical Immunogenetics, The Univeristy of Texas Health Science Center at Houston, Houston, TX, USA. (författare)
Vilá, Luis M.University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, USA. (författare)
Petri, MichelleDivision of Rheumatology, Johns Hopkins, Baltimore, MD, USA. (författare)
Ramsey-Goldman, RosalindDivision of Rheumatology, Northwestern University, Chicago, IL, USA. (författare)
Freedman, Barry I.Wake Forest School of Medicine, Winston-Salem, NC, USA. (författare)
Niewold, TimothyDivision of Rheumatology and Immunology, Mayo Clinic, Rochester, MN, USA. (författare)
Stevens, Anne M.University of Washington and Seattle Childrens Hospital, Seattle, WA, USA. (författare)
Tsao, Betty P.David Geffen School of Medicine, University of California, Los Angeles, CA, USA. (författare)
Ying, JunMD Anderson Cancer Center, University of Texas, Houston, TX, USA. (författare)
Mayes, Maureen D.MD Anderson Cancer Center, University of Texas, Houston, TX, USA. (författare)
Gorlova, Olga Y.MD Anderson Cancer Center, University of Texas, Houston, TX, USA. (författare)
Wakeland, WardUniversity of Texas Southwestern Medical School, Dallas, TX, USA. (författare)
Radstake, TimothyDepartment of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. (författare)
Martin, EzequielInstituto de Parasitología y Biomedicina López Neyra Avda, Granada, Spain and. (författare)
Martin, JavierInstituto de Parasitología y Biomedicina López Neyra Avda, Granada, Spain and. (författare)
Siminovitch, KatherineMount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, ON, Canada Department of Medicine, University of Toronto, Toronto, ON, Canada. (författare)
Moser Sivils, Kathy L.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Gaffney, Patrick M.Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. (författare)
Langefeld, Carl D.Department of Biostatistical Sciences and Center for Public Health Genomics and. (författare)
Harley, John B.Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA. (författare)
Kaufman, Kenneth M.Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA. (författare)
Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USALiver Centre, Toronto Western Hospital, Toronto, ON, Canada. (creator_code:org_t)

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Ingår i:Human Molecular Genetics: Oxford University Press (OUP)24:2, s. 582-5960964-69061460-2083

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Av författaren/redakt...: Kottyan, Leah C.; Zoller, Erin E.; Bene, Jessica; Lu, Xiaoming; Kelly, Jennifer ...; Rupert, Andrew M ...; visa fler...; Lessard, Christo ...; Vaughn, Samuel E ...; Marion, Miranda; Weirauch, Matthe ...; Namjou, Bahram; Adler, Adam; Rasmussen, Astri ...; Glenn, Stuart; Montgomery, Cour ...; Hirschfield, Gid ...; Xie, Gang; Coltescu, Catali ...; Amos, Chris; Li, He; Ice, John A.; Nath, Swapan K.; Mariette, Xavier; Bowman, Simon; Rischmueller, Ma ...; Lester, Sue; Brun, Johan G.; Gøransson, Lasse ...; Harboe, Erna; Omdal, Roald; Cunninghame-Grah ...; Vyse, Tim; Miceli-Richard, ...; Brennan, Michael ...; Lessard, James A ...; Wahren-Herlenius ...; Kvarnström, Mari ...; Illei, Gabor G.; Witte, Torsten; Jonsson, Roland; Eriksson, Per, 1 ...; Nordmark, Gunnel; Ng, Wan-Fai; Anaya, Juan-Manu ...; Rhodus, Nelson N ...; Segal, Barbara M ...; Merrill, Joan T.; James, Judith A.; Guthridge, Joel ...; Hal Scofield, R; Alarcon-Riquelme ...; Bae, Sang-Cheol; Boackle, Susan A ...; Criswell, Lindse ...; Gilkeson, Gary; Kamen, Diane L; Jacob, Chaim O.; Kimberly, Robert; Brown, Elizabeth; Edberg, Jeffrey; Alarcón, Graciel ...; Reveille, John D ...; Vilá, Luis M.; Petri, Michelle; Ramsey-Goldman, ...; Freedman, Barry ...; Niewold, Timothy; Stevens, Anne M.; Tsao, Betty P.; Ying, Jun; Mayes, Maureen D ...; Gorlova, Olga Y.; Wakeland, Ward; Radstake, Timoth ...; Martin, Ezequiel; Martin, Javier; Siminovitch, Kat ...; Moser Sivils, Ka ...; Gaffney, Patrick ...; Langefeld, Carl ...; Harley, John B.; Kaufman, Kenneth ...; visa färre...

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