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Transancestral mapping and genetic load in systemic lupus erythematosus

Author

Listed:
  • Carl D. Langefeld

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Hannah C. Ainsworth

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Deborah S. Cunninghame Graham

    (Infection and Inflammatory Diseases, King’s College London, Guy’s Hospital)

  • Jennifer A. Kelly

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation)

  • Mary E. Comeau

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Miranda C. Marion

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Timothy D. Howard

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Center for Human Genomics and Personalized Medicine Research, Wake Forest School of Medicine)

  • Paula S. Ramos

    (Medical University of South Carolina
    Medical University of South Carolina)

  • Jennifer A. Croker

    (UAB School of Medicine)

  • David L. Morris

    (Infection and Inflammatory Diseases, King’s College London, Guy’s Hospital)

  • Johanna K. Sandling

    (Molecular Medicine and Science for Life Laboratory, Uppsala University)

  • Jonas Carlsson Almlöf

    (Molecular Medicine and Science for Life Laboratory, Uppsala University)

  • Eduardo M. Acevedo-Vásquez

    (Hospital G. Almenara y Facultad de Medicina, Universidad Nacional Mayor de San Marcos)

  • Graciela S. Alarcón

    (UAB School of Medicine)

  • Alejandra M. Babini

    (Hospital Italiano de Córdoba)

  • Vicente Baca

    (Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social)

  • Anders A. Bengtsson

    (Rheumatology, Lund University)

  • Guillermo A. Berbotto

    (Hospital Eva Perón)

  • Marc Bijl

    (Martini Hospital)

  • Elizabeth E. Brown

    (UAB School of Medicine)

  • Hermine I. Brunner

    (Cincinnati Children’s Hospital Medical Center and the University of Cincinnati)

  • Mario H. Cardiel

    (Centro de Investigación Clínica de Morelia)

  • Luis Catoggio

    (Hospital Italiano de Buenos Aires)

  • Ricard Cervera

    (Hospital Clínic, University of Barcelona)

  • Jorge M. Cucho-Venegas

    (Hospital G. Almenara y Facultad de Medicina, Universidad Nacional Mayor de San Marcos)

  • Solbritt Rantapää Dahlqvist

    (Umeå University)

  • Sandra D’Alfonso

    (University of Eastern Piedmont)

  • Berta Martins Da Silva

    (Unidade Multidisciplinar em Investigação Biomédica/Instituto de Ciências Biomédicas de Abel Salazar—Universidade do Porto)

  • Iñigo de la Rúa Figueroa

    (Hospital Universitario de Gran Canaria Dr Negrín)

  • Andrea Doria

    (University of Padua)

  • Jeffrey C. Edberg

    (UAB School of Medicine)

  • Emőke Endreffy

    (Albert Szent-Györgyi Medical Center, Faculty of Medicine, University of Szeged)

  • Jorge A. Esquivel-Valerio

    (Hospital Universitario ‘Dr José Eleuterio González’ Universidad Autonoma de Nuevo León)

  • Paul R. Fortin

    (CHU de Québec Université Laval)

  • Barry I. Freedman

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Section on Nephrology, Wake Forest School of Medicine)

  • Johan Frostegård

    (Institute of Environmental Medicine, Unit of Immunology and Chronic diseases, Karolinska Institutet)

  • Mercedes A. García

    (Hospital Interzonal General de Agudos General San Martín)

  • Ignacio García de la Torre

    (University of Guadalajara)

  • Gary S. Gilkeson

    (Medical University of South Carolina)

  • Dafna D. Gladman

    (Centre for Prognosis Studies in The Rheumatic Diseases, Krembil Research Institute, Toronto Western Hospital)

  • Iva Gunnarsson

    (Unit of Rheumatology, Karolinska Institutet, Karolinska University Hospital)

  • Joel M. Guthridge

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation)

  • Jennifer L. Huggins

    (Cincinnati Children’s Hospital Medical Center and the University of Cincinnati)

  • Judith A. James

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation
    University of Oklahoma Health Sciences Center)

  • Cees G. M. Kallenberg

    (Department of Rheumatology and Clinical Immunology,University Medical Center Groningen,University of Groningen)

  • Diane L. Kamen

    (Medical University of South Carolina)

  • David R. Karp

    (University of Texas SouthWestern Medical Center)

  • Kenneth M. Kaufman

    (Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center)

  • Leah C. Kottyan

    (Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center)

  • László Kovács

    (Albert Szent-Györgyi Medical Centre, University of Szeged)

  • Helle Laustrup

    (Odense University Hospital)

  • Bernard R. Lauwerys

    (Rheumatology, Cliniques Universitaires Saint-Luc & Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain)

  • Quan-Zhen Li

    (University of Texas SouthWestern Medical Center)

  • Marco A. Maradiaga-Ceceña

    (Hospital General de Culiacán)

  • Javier Martín

    (Instituto de Parasitología y Biomedicina López Neyra, CSIC)

  • Joseph M. McCune

    (University of Michigan Medical Center)

  • David R. McWilliams

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Joan T. Merrill

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation)

  • Pedro Miranda

    (Centro de Estudios Reumatológicos, Santiago de Chile)

  • José F. Moctezuma

    (Hospital General de México)

  • Swapan K. Nath

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation)

  • Timothy B. Niewold

    (Mayo Clinic)

  • Lorena Orozco

    (Instituto Nacional de Medicina Genómica (INMEGEN))

  • Norberto Ortego-Centeno

    (Unidad de Enfermedades Autoimmunes Sistémicas, UGC Medicina Interna, Hospital Universitario San Cecilio)

  • Michelle Petri

    (Johns Hopkins University School of Medicine)

  • Christian A. Pineau

    (McGill University)

  • Bernardo A. Pons-Estel

    (Sanatorio Parque)

  • Janet Pope

    (University of Western Ontario)

  • Prithvi Raj

    (University of Texas SouthWestern Medical Center)

  • Rosalind Ramsey-Goldman

    (Northwestern University Feinberg School of Medicine)

  • John D. Reveille

    (The University of Texas Health Science Center at Houston (UTHealth) Medical School)

  • Laurie P. Russell

    (Center for Public Health Genomics, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • José M. Sabio

    (Hospital Universitario Virgen de las Nieves)

  • Carlos A. Aguilar-Salinas

    (Instituto Nacional de Ciencias Médicas y Nutrición)

  • Hugo R. Scherbarth

    (Unidad Reumatología y Enfermedades Autoinmunes H.I.G.A. Dr Alende Mar del Plata)

  • Raffaella Scorza

    (Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca'Granda Ospedale Ma Repiore Policlinico and University of Milan)

  • Michael F. Seldin

    (UC Davis School of Medicine)

  • Christopher Sjöwall

    (Linköping University)

  • Elisabet Svenungsson

    (Unit of Rheumatology, Karolinska Institutet, Karolinska University Hospital)

  • Susan D. Thompson

    (Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center)

  • Sergio M. A. Toloza

    (Ministry of Health, San Fernando del Valle de Catamarca)

  • Lennart Truedsson

    (Section of Microbiology, Immunology and Glycobiology, Lund University)

  • Teresa Tusié-Luna

    (Unidad de Biología Molecular y Medicina Genómica Instituto de Investigaciones Biomédicas/UNAM Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán)

  • Carlos Vasconcelos

    (Hospital Santo Antonio, Universidade do Porto)

  • Luis M. Vilá

    (University of Puerto Rico School of Medicine)

  • Daniel J. Wallace

    (Cedars Sinai Medical Center)

  • Michael H. Weisman

    (Cedars Sinai Medical Center)

  • Joan E. Wither

    (Centre for Prognosis Studies in The Rheumatic Diseases, Krembil Research Institute, Toronto Western Hospital)

  • Tushar Bhangale

    (Human Genetics, Genentech Inc, South San Francisco)

  • Jorge R. Oksenberg

    (University of California at San Francisco)

  • John D. Rioux

    (Université de Montréal and the Montreal Heart Institute)

  • Peter K. Gregersen

    (Center for Genomics & Human Genetics, The Feinstein Institute for Medical Research)

  • Ann-Christine Syvänen

    (Molecular Medicine and Science for Life Laboratory, Uppsala University)

  • Lars Rönnblom

    (Rheumatology, Uppsala University)

  • Lindsey A. Criswell

    (Rosalind Russell/Ephraim P Engleman Rheumatology Research Center, UCSF School of Medicine)

  • Chaim O. Jacob

    (Keck School of Medicine of USC)

  • Kathy L. Sivils

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation)

  • Betty P. Tsao

    (Medical University of South Carolina)

  • Laura E. Schanberg

    (Duke University)

  • Timothy W. Behrens

    (Human Genetics, Genentech Inc, South San Francisco)

  • Earl D. Silverman

    (The Hospital for Sick Children, Hospital for Sick Children Research Institute and University of Toronto)

  • Marta E. Alarcón-Riquelme

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation
    Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO)
    Unit of Institute of Environmental Medicine, Karolinska Institute)

  • Robert P. Kimberly

    (UAB School of Medicine)

  • John B. Harley

    (Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center)

  • Edward K. Wakeland

    (University of Texas SouthWestern Medical Center)

  • Robert R. Graham

    (Human Genetics, Genentech Inc, South San Francisco)

  • Patrick M. Gaffney

    (Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation)

  • Timothy J. Vyse

    (Infection and Inflammatory Diseases, King’s College London, Guy’s Hospital)

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P

Suggested Citation

  • Carl D. Langefeld & Hannah C. Ainsworth & Deborah S. Cunninghame Graham & Jennifer A. Kelly & Mary E. Comeau & Miranda C. Marion & Timothy D. Howard & Paula S. Ramos & Jennifer A. Croker & David L. Mo, 2017. "Transancestral mapping and genetic load in systemic lupus erythematosus," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16021
    DOI: 10.1038/ncomms16021
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    Cited by:

    1. Laura Lau & Taryn A. Cariaga & Abraham B. Chang & Joan H. Lane & Whitney E. Purtha & Aaron S. Rapaport & Ruozhen Hu & Hiroyasu Konno & Daryl N. Bulloch & Matthew J. Rardin & Bradford W. Gibson & Jason, 2025. "An essential role for TASL in mouse autoimmune pathogenesis and Toll-like receptor signaling," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    2. Ales Drobek & Léa Bernaleau & Maeva Delacrétaz & Sandra Calderon Copete & Claire Royer-Chardon & Mélissa Longepierre & Marta Monguió-Tortajada & Jakub Korzeniowski & Samuel Rotman & Julien Marquis & M, 2025. "The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    3. Chachrit Khunsriraksakul & Qinmengge Li & Havell Markus & Matthew T. Patrick & Renan Sauteraud & Daniel McGuire & Xingyan Wang & Chen Wang & Lida Wang & Siyuan Chen & Ganesh Shenoy & Bingshan Li & Xue, 2023. "Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Andras Boeszoermenyi & Léa Bernaleau & Xudong Chen & Felix Kartnig & Min Xie & Haobo Zhang & Sensen Zhang & Maeva Delacrétaz & Anna Koren & Ann-Katrin Hopp & Vojtech Dvorak & Stefan Kubicek & Daniel A, 2023. "A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Younghun Han & Jinyoung Byun & Catherine Zhu & Ryan Sun & Julia Y. Roh & Heather J. Cordell & Hyun-Sung Lee & Vikram R. Shaw & Sung Wook Kang & Javad Razjouyan & Matthew A. Cooley & Manal M. Hassan & , 2023. "Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Angela Andaleon & Lauren S Mogil & Heather E Wheeler, 2019. "Genetically regulated gene expression underlies lipid traits in Hispanic cohorts," PLOS ONE, Public Library of Science, vol. 14(8), pages 1-21, August.
    7. Antje Häder & Sascha Schäuble & Jan Gehlen & Nadja Thielemann & Benedikt C. Buerfent & Vitalia Schüller & Timo Hess & Thomas Wolf & Julia Schröder & Michael Weber & Kerstin Hünniger & Jürgen Löffler &, 2023. "Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Peter J. Eggenhuizen & Rachel M. Y. Cheong & Cecilia Lo & Janet Chang & Boaz H. Ng & Yi Tian Ting & Julie A. Monk & Khai L. Loh & Ashraf Broury & Elean S. V. Tay & Chanjuan Shen & Yong Zhong & Steven , 2024. "Smith-specific regulatory T cells halt the progression of lupus nephritis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Qiang Wang & Taehyeung Kim & Marta Martínez-Bonet & Vitor R. C. Aguiar & Sangwan Sim & Jing Cui & Jeffrey A. Sparks & Xiaoting Chen & Marc Todd & Brian Wauford & Miranda C. Marion & Carl D. Langefeld , 2024. "High-throughput identification of functional regulatory SNPs in systemic lupus erythematosus," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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