Transancestral mapping and genetic load in systemic lupus erythematosus View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-07-17

AUTHORS

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. Morris, Johanna K. Sandling, Jonas Carlsson Almlöf, Eduardo M. Acevedo-Vásquez, Graciela S. Alarcón, Alejandra M. Babini, Vicente Baca, Anders A. Bengtsson, Guillermo A. Berbotto, Marc Bijl, Elizabeth E. Brown, Hermine I. Brunner, Mario H. Cardiel, Luis Catoggio, Ricard Cervera, Jorge M. Cucho-Venegas, Solbritt Rantapää Dahlqvist, Sandra D’Alfonso, Berta Martins Da Silva, Iñigo de la Rúa Figueroa, Andrea Doria, Jeffrey C. Edberg, Emőke Endreffy, Jorge A. Esquivel-Valerio, Paul R. Fortin, Barry I. Freedman, Johan Frostegård, Mercedes A. García, Ignacio García de la Torre, Gary S. Gilkeson, Dafna D. Gladman, Iva Gunnarsson, Joel M. Guthridge, Jennifer L. Huggins, Judith A. James, Cees G. M. Kallenberg, Diane L. Kamen, David R. Karp, Kenneth M. Kaufman, Leah C. Kottyan, László Kovács, Helle Laustrup, Bernard R. Lauwerys, Quan-Zhen Li, Marco A. Maradiaga-Ceceña, Javier Martín, Joseph M. McCune, David R. McWilliams, Joan T. Merrill, Pedro Miranda, José F. Moctezuma, Swapan K. Nath, Timothy B. Niewold, Lorena Orozco, Norberto Ortego-Centeno, Michelle Petri, Christian A. Pineau, Bernardo A. Pons-Estel, Janet Pope, Prithvi Raj, Rosalind Ramsey-Goldman, John D. Reveille, Laurie P. Russell, José M. Sabio, Carlos A. Aguilar-Salinas, Hugo R. Scherbarth, Raffaella Scorza, Michael F. Seldin, Christopher Sjöwall, Elisabet Svenungsson, Susan D. Thompson, Sergio M. A. Toloza, Lennart Truedsson, Teresa Tusié-Luna, Carlos Vasconcelos, Luis M. Vilá, Daniel J. Wallace, Michael H. Weisman, Joan E. Wither, Tushar Bhangale, Jorge R. Oksenberg, John D. Rioux, Peter K. Gregersen, Ann-Christine Syvänen, Lars Rönnblom, Lindsey A. Criswell, Chaim O. Jacob, Kathy L. Sivils, Betty P. Tsao, Laura E. Schanberg, Timothy W. Behrens, Earl D. Silverman, Timothy J. Vyse, Robert R. Graham, Edward K. Wakeland, Robert P. Kimberly, John B. Harley, Patrick M. Gaffney, Marta E. Alarcón-Riquelme

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<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE. More... »

PAGES

16021

References to SciGraph publications

Journal

TITLE

Nature Communications

ISSUE

N/A

VOLUME

8

Author Affiliations

  • Wake Forest University
  • King's College London
  • Oklahoma Medical Research Foundation
  • Medical University of South Carolina
  • University of Alabama at Birmingham
  • Uppsala University
  • National University of San Marcos
  • Centro Medico Nacional Siglo XXI
  • Lund University
  • Martini Ziekenhuis
  • University of Cincinnati
  • Hospital Italiano de Buenos Aires
  • Umeå University
  • University of Eastern Piedmont Amadeo Avogadro
  • University of Porto
  • Hospital Universitario de Gran Canaria Doctor Negrín
  • University of Padua
  • University of Szeged
  • Hospital Universitario Dr José Eleuterio Gonzalez
  • Centre Hospitalier Universitaire de Québec
  • Karolinska Institute
  • University of Guadalajara
  • University of Oklahoma Health Sciences Center
  • The University of Texas Southwestern Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Odense University Hospital
  • Université Catholique de Louvain
  • Institute of Parasitology and Biomedicine "López-Neyra"
  • Michigan Medicine
  • Hospital General de México
  • Mayo Clinic
  • National Institute of Genomic Medicine
  • Complejo Hospitalario Universitario de Granada
  • Johns Hopkins University
  • McGill University
  • Western University
  • Northwestern University
  • The University of Texas Health Science Center at Houston
  • Hospital Universitario Virgen de las Nieves
  • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
  • University of Milan
  • University of California, Davis
  • Linköping University
  • University of Puerto Rico System
  • Cedars-Sinai Medical Center
  • Roche (United States)
  • University of California, San Francisco
  • University of Montreal
  • Feinstein Institute for Medical Research
  • University of Southern California
  • Duke University
  • University of Toronto
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms16021

    DOI

    http://dx.doi.org/10.1038/ncomms16021

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1090739403

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28714469


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    N-Triples is a line-based linked data format ideal for batch operations.

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