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Research Article

Admixture Mapping in Lupus Identifies Multiple Functional Variants within IFIH1 Associated with Apoptosis, Inflammation, and Autoantibody Production

  • Julio E. Molineros equal contributor,

    equal contributor Contributed equally to this work with: Julio E. Molineros, Amit K. Maiti, Celi Sun

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Amit K. Maiti equal contributor,

    equal contributor Contributed equally to this work with: Julio E. Molineros, Amit K. Maiti, Celi Sun

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Celi Sun equal contributor,

    equal contributor Contributed equally to this work with: Julio E. Molineros, Amit K. Maiti, Celi Sun

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Loren L. Looger,

    Affiliation: Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia, United States of America

    X
  • Shizhong Han,

    Affiliations: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, United States of America

    X
  • Xana Kim-Howard,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Stuart Glenn,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Adam Adler,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Jennifer A. Kelly,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Timothy B. Niewold,

    Affiliation: Mayo Clinic, Division of Rheumatology and Department of Immunology, Rochester, Minnesota, United States of America

    X
  • Gary S. Gilkeson,

    Affiliation: Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, United States of America

    X
  • Elizabeth E. Brown,

    Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

    X
  • Graciela S. Alarcón,

    Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

    X
  • Jeffrey C. Edberg,

    Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

    X
  • Michelle Petri,

    Affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America

    X
  • Rosalind Ramsey-Goldman,

    Affiliation: Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America

    X
  • John D. Reveille,

    Affiliation: Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, United States of America

    X
  • Luis M. Vilá,

    Affiliation: Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

    X
  • Barry I. Freedman,

    Affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America

    X
  • Betty P. Tsao,

    Affiliation: Division of Rheumatology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America

    X
  • Lindsey A. Criswell,

    Affiliation: Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, California, United States of America

    X
  • Chaim O. Jacob,

    Affiliation: Department of Medicine, University of Southern California, Los Angeles, California, United States of America

    X
  • Jason H. Moore,

    Affiliation: Department of Genetics, Dartmouth Medical School, Lebanon, New Hampshire, United States of America

    X
  • Timothy J. Vyse,

    Affiliations: Division of Genetics and Molecular Medicine, King's College London, London, United Kingdom, Division of Immunology, Infection and Inflammatory Diseases, Kings College London, London, United Kingdom

    X
  • Carl L. Langefeld,

    Affiliation: Department of Biostatistical Sciences, Wake Forest University Health Sciences, Wake Forest, North Carolina, United States of America

    X
  • Joel M. Guthridge,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Patrick M. Gaffney,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Kathy L. Moser,

    Affiliations: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America

    X
  • R. Hal Scofield,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Marta E. Alarcón-Riquelme,

    Affiliations: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America, Centro de Genómica e Investigación Oncológica (GENyO)–Pfizer/Universidad de Granada/Junta de Andalucía, Granada, Spain

    X
  • on behalf of the BIOLUPUS Network,

    Membership of the BIOLUPUS Network is available in Text S1.

    X
  • Scott M. Williams,

    Affiliation: Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America

    X
  • Joan T. Merrill,

    Affiliation: Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Judith A. James,

    Affiliations: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America

    X
  • Kenneth M. Kaufman,

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Robert P. Kimberly,

    Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America

    X
  • John B. Harley,

    Affiliation: Cincinnati Children's Hospital Medical Center and the U.S. Department of Veterans Affairs Medical Center, Cincinnati, Ohio, United States of America

    X
  • Swapan K. Nath mail

    Swapan-Nath@omrf.org

    Affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America

    X
  • Published: February 18, 2013
  • DOI: 10.1371/journal.pgen.1003222

About the Authors

Julio E. Molineros, Amit K. Maiti, Celi Sun, Shizhong Han, Xana Kim-Howard, Stuart Glenn, Adam Adler, Jennifer A. Kelly, Joel M. Guthridge, Patrick M. Gaffney, Kathy L. Moser, R. Hal Scofield, Marta E. Alarcón-Riquelme, Judith A. James, Kenneth M. Kaufman, Swapan K. Nath
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America
Loren L. Looger
Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia, United States of America
Shizhong Han
Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, United States of America
Timothy B. Niewold
Mayo Clinic, Division of Rheumatology and Department of Immunology, Rochester, Minnesota, United States of America
Gary S. Gilkeson
Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, United States of America
Elizabeth E. Brown, Graciela S. Alarcón, Jeffrey C. Edberg, Robert P. Kimberly
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
Michelle Petri
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Rosalind Ramsey-Goldman
Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
John D. Reveille
Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, United States of America
Luis M. Vilá
Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
Barry I. Freedman
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America
Betty P. Tsao
Division of Rheumatology, Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
Lindsey A. Criswell
Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, California, United States of America
Chaim O. Jacob
Department of Medicine, University of Southern California, Los Angeles, California, United States of America
Jason H. Moore
Department of Genetics, Dartmouth Medical School, Lebanon, New Hampshire, United States of America
Timothy J. Vyse
Division of Genetics and Molecular Medicine, King's College London, London, United Kingdom
Timothy J. Vyse
Division of Immunology, Infection and Inflammatory Diseases, Kings College London, London, United Kingdom
Carl L. Langefeld
Department of Biostatistical Sciences, Wake Forest University Health Sciences, Wake Forest, North Carolina, United States of America
Kathy L. Moser, Judith A. James
College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
Marta E. Alarcón-Riquelme
Centro de Genómica e Investigación Oncológica (GENyO)–Pfizer/Universidad de Granada/Junta de Andalucía, Granada, Spain
Scott M. Williams
Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America
Joan T. Merrill
Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America
John B. Harley
Cincinnati Children's Hospital Medical Center and the U.S. Department of Veterans Affairs Medical Center, Cincinnati, Ohio, United States of America

Corresponding Author

Email: Swapan-Nath@omrf.org

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: SKN. Performed the experiments: AKM JEM. Analyzed the data: JEM CS SH SG XK-H LLL. Contributed reagents/materials/analysis tools: JBH KMK JAK AA SG CS CLL PMG JAJ MEA-R TBN EEB RR-G GSA MP JDR LMV BPT BIF LAC COJ KLM JCE JMG TJV GSG JTM JHM SMW RHS RPK. Wrote the paper: JEM AKM LLL SKN.