title: GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.
abstract: In a genome-wide association study (GWAS) of individuals of European ancestry afflicted with systemic lupus erythematosus (SLE) the extensive utilization of imputation, step-wise multiple regression, lasso regularization and increasing study power by utilizing false discovery rate instead of a Bonferroni multiple test correction enabled us to identify 13 novel non-human leukocyte antigen (HLA) genes and confirmed the association of four genes previously reported to be associated. Novel genes associated with SLE susceptibility included two transcription factors (EHF and MED1), two components of the NF-κB pathway (RASSF2 and RNF114), one gene involved in adhesion and endothelial migration (CNTN6) and two genes involved in antigen presentation (BIN1 and SEC61G). In addition, the strongly significant association of multiple single-nucleotide polymorphisms (SNPs) in the HLA region was assigned to HLA alleles and serotypes and deconvoluted into four primary signals. The novel SLE-associated genes point to new directions for both the diagnosis and treatment of this debilitating autoimmune disease.
authors.affiliation: 1] The Lupus Genetic Group, Department of Medicine, University of Southern California, Los Angeles, CA, USA [2] Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Armstrong
authors.affiliation: 1] The Lupus Genetic Group, Department of Medicine, University of Southern California, Los Angeles, CA, USA [2] Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Zidovetzki
authors.affiliation: 1] Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA [2] Centro de Genómica e Investigación Oncológica (GENYO), Pfizer-Universidad de Granada-Junta de Andalucia, Granada, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.affiliation: Division of Rheumatology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Tsao
authors.affiliation: Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Criswell
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Kimberly
authors.affiliation: 1] Division of Rheumatology and The Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] U.S. Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Harley
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Sivils
authors.affiliation: Divisions of Genetics and Molecular Medicine and Immunology, King's College London, London, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Vyse
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Gaffney
authors.affiliation: Department of Biostatistical Sciences, Wake Forest University Health Sciences, Wake Forest, NC, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Langefeld
authors.affiliation: The Lupus Genetic Group, Department of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: C O
authors.initials: CO
authors.lastname: Jacob
mesh_terms: D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis
chemical_list: D006680:HLA Antigens