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SCI Article

Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythemat
Author Bae, Sang-Cheol (Dept Rheumatol); Cho, Soo-Kyung (Dept Rheumatol); Kim, Jae-Hoon (Dept Rheumatol); Park, So-Yeon (Dept Rheumatol);
Corresponding Author Info Moser, KL (reprint author), Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
E-mail 씠硫붿씪 븘씠肄
Document Type Article
Source AMERICAN JOURNAL OF HUMAN GENETICS Volume:90 Issue:4 Pages:648-660 Published:2012
Times Cited 50
External Information PDF 븘씠肄http://dx.doi.org/10.1016/j.ajhg.2012.02.023
Abstract Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p(meta-Euro) = 2.08 x 10(-10)), transmembrane protein 39A (TMEM39A; rs1132200; p(meta-all) 8.62 x 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48 x 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 x 10(-8)
Web of Science Categories Genetics & Heredity
Funding
Language English
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