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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 07 2022
Historique:
received: 27 09 2021
accepted: 17 05 2022
entrez: 27 7 2022
pubmed: 28 7 2022
medline: 30 7 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35896530
doi: 10.1038/s41467-022-30773-y
pii: 10.1038/s41467-022-30773-y
pmc: PMC9329286
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

4287

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR073855
Pays : United States
Organisme : NIDCR NIH HHS
ID : R21 DE029303
Pays : United States
Organisme : Department of Health
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn
Type : ErratumIn

Informations de copyright

© 2022. The Author(s).

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Auteurs

Bhuwan Khatri (B)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Kandice L Tessneer (KL)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Astrid Rasmussen (A)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Farhang Aghakhanian (F)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Tove Ragna 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.

Adam Adler (A)

NGS Core Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Ilias Alevizos (I)

Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.

Juan-Manuel Anaya (JM)

Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia.

Lara A 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.

Eva Baecklund (E)

Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Johan G Brun (JG)

Department of Clinical Science, University of Bergen, Bergen, Norway.

Sara Magnusson Bucher (SM)

Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

Maija-Leena Eloranta (ML)

Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Fiona Engelke (F)

Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.

Helena Forsblad-d'Elia (H)

Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Stuart B Glenn (SB)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Daniel Hammenfors (D)

Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.

Juliana Imgenberg-Kreuz (J)

Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Janicke Liaaen Jensen (JL)

Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Svein Joar Auglænd Johnsen (SJA)

Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway.

Malin V 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.

Marika 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.

Jennifer A Kelly (JA)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

He 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.

Thomas Mandl (T)

Rheumatology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.

Javier Martín (J)

Instituto de Biomedicina y Parasitología López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.

Gaétane 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.

Katrine Brække Norheim (KB)

Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Rheumatology, Stavanger University Hospital, Stavanger, Norway.

Øyvind Palm (Ø)

Department of Rheumatology, University of Oslo, Oslo, Norway.

Kathrine Skarstein (K)

Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Pathology, Haukeland University Hospital, Bergen, Norway.

Anna M Stolarczyk (AM)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Kimberly E Taylor (KE)

Department of Medicine, Russell/Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, California, USA.

Maria Teruel (M)

Genyo, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.

Elke Theander (E)

Department of Rheumatology, Skåne University Hospital, Malmö, Sweden.
Medical Affairs, Jannsen-Cilag EMEA (Europe/Middle East/Africa), Beerse, Belgium.

Swamy 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.

Daniel J 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.

Kiely M Grundahl (KM)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Kimberly S Hefner (KS)

Hefner Eye Care and Optical Center, Oklahoma City, OK, USA.

Lida Radfar (L)

Oral Diagnosis and Radiology Department, University of Oklahoma College of Dentistry, Oklahoma City, OK, USA.

David M Lewis (DM)

Department of Oral and Maxillofacial Pathology, University of Oklahoma College of Dentistry, Oklahoma City, OK, USA.

Donald U Stone (DU)

Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

C Erick Kaufman (CE)

Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Michael T 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.

Joel M 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.

Judith A 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.

R Hal 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.

Patrick M Gaffney (PM)

Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Lindsey A 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.

Roland Jonsson (R)

Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.

Per Eriksson (P)

Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.

Simon J 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.

Roald Omdal (R)

Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Internal Medicine, Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway.

Lars Rönnblom (L)

Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Blake Warner (B)

Salivary Disorder Unit, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.

Maureen Rischmueller (M)

Rheumatology Department, The Queen Elizabeth Hospital, Woodville, South Australia.
University of Adelaide, Adelaide, South Australia.

Torsten Witte (T)

Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.

A Darise Farris (AD)

Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Xavier 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.

Marta E Alarcon-Riquelme (ME)

Genyo, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.

Caroline H Shiboski (CH)

Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA, USA.

Marie Wahren-Herlenius (M)

Department of Clinical Science, University of Bergen, Bergen, Norway.
Rheumatology Unity, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

Wan-Fai 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.

Kathy L 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.

Indra Adrianto (I)

Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.

Gunnel Nordmark (G)

Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Christopher J 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.

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