Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.

Autor: Khatri B; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Tessneer KL; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Rasmussen A; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Aghakhanian F; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Reksten TR; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.; Department of Clinical Science, University of Bergen, Bergen, Norway., Adler A; NGS Core Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Alevizos I; Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA., Anaya JM; Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia., Aqrawi LA; Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.; Department of Health Sciences, Kristiania University College, Oslo, Norway., Baecklund E; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Brun JG; Department of Clinical Science, University of Bergen, Bergen, Norway., Bucher SM; Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden., Eloranta ML; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Engelke F; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany., Forsblad-d'Elia H; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden., Glenn SB; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Hammenfors D; Department of Rheumatology, Haukeland University Hospital, Bergen, Norway., Imgenberg-Kreuz J; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Jensen JL; Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway., Johnsen SJA; Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway., Jonsson MV; Department of Clinical Science, University of Bergen, Bergen, Norway.; Section for Oral and Maxillofacial Radiology, Department of Clinical Dentistry, Medical Faculty, University of Bergen, Bergen, Norway., Kvarnström M; Rheumatology Unity, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.; Academic Specialist Center, Center for Rheumatology and Studieenheten, Stockholm Health Services, Region Stockholm, Sweden., Kelly JA; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Li H; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.; Translational Sciences, The Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, PA, USA., Mandl T; Rheumatology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden., Martín J; Instituto de Biomedicina y Parasitología López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain., Nocturne G; Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1184, Le Kremlin Bicêtre, France., Norheim KB; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Rheumatology, Stavanger University Hospital, Stavanger, Norway., Palm Ø; Department of Rheumatology, University of Oslo, Oslo, Norway., Skarstein K; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Pathology, Haukeland University Hospital, Bergen, Norway., Stolarczyk AM; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Taylor KE; Department of Medicine, Russell/Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, California, USA., Teruel M; Genyo, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain., Theander E; Department of Rheumatology, Skåne University Hospital, Malmö, Sweden.; Medical Affairs, Jannsen-Cilag EMEA (Europe/Middle East/Africa), Beerse, Belgium., Venuturupalli S; Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Wallace DJ; Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Grundahl KM; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Hefner KS; Hefner Eye Care and Optical Center, Oklahoma City, OK, USA., Radfar L; Oral Diagnosis and Radiology Department, University of Oklahoma College of Dentistry, Oklahoma City, OK, USA., Lewis DM; Department of Oral and Maxillofacial Pathology, University of Oklahoma College of Dentistry, Oklahoma City, OK, USA., Stone DU; Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Kaufman CE; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Brennan MT; Department of Oral Medicine/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA.; Department of Otolaryngology/Head and Neck Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA., Guthridge JM; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., James JA; 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., Scofield RH; 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.; US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA., Gaffney PM; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Criswell LA; Department of Medicine, Russell/Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, California, USA.; Institute of Human Genetics (IHG), University of California San Francisco, San Francisco, CA, USA.; Genomics of Autoimmune Rheumatic Disease Section, National Human Genome Research Institute, NIH, Bethesda, MD, USA., Jonsson R; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Rheumatology, Haukeland University Hospital, Bergen, Norway., Eriksson P; Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden., Bowman SJ; Rheumatology Department, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.; Rheumatology Research Group, Institute of Inflammation & Ageing, University of Birmingham, Birmingham, UK.; Rheumatology Department, Milton Keynes University Hospital, Milton Keynes, UK., Omdal R; Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway., Rönnblom L; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Warner B; Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA., Rischmueller M; Rheumatology Department, The Queen Elizabeth Hospital, Woodville, South Australia.; University of Adelaide, Adelaide, South Australia., Witte T; Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany., Farris AD; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Mariette X; Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1184, Le Kremlin Bicêtre, France., Alarcon-Riquelme ME; Genyo, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain., Shiboski CH; Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA., Wahren-Herlenius M; Department of Clinical Science, University of Bergen, Bergen, Norway.; Rheumatology Unity, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden., Ng WF; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.; NIHR Newcastle Biomedical Centre and NIHR Newcastle Clinical Research Facility, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Sivils KL; Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.; Translational Sciences, The Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, PA, USA., Adrianto I; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA., Nordmark G; Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Lessard CJ; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. chris-lessard@omrf.org.; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. chris-lessard@omrf.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jul 27; Vol. 13 (1), pp. 4287. Date of Electronic Publication: 2022 Jul 27.
DOI: 10.1038/s41467-022-30773-y
Abstrakt: Sjögren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.
(© 2022. The Author(s).)
Databáze: MEDLINE
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