Letter abstract
Nature Genetics 41, 1228 - 1233 (2009)
Published online: 18 October 2009 | doi:10.1038/ng.468
A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
Vesela Gateva1, Johanna K Sandling2, Geoff Hom1, Kimberly E Taylor3, Sharon A Chung3, Xin Sun1, Ward Ortmann1, Roman Kosoy4, Ricardo C Ferreira1, Gunnel Nordmark5, Iva Gunnarsson6, Elisabet Svenungsson6, Leonid Padyukov6, Gunnar Sturfelt7, Andreas Jönsen7, Anders A Bengtsson7, Solbritt Rantapää-Dahlqvist8, Emily C Baechler9, Elizabeth E Brown10, Graciela S Alarcón10, Jeffrey C Edberg10, Rosalind Ramsey-Goldman11, Gerald McGwin Jr10, John D Reveille12, Luis M Vilá13, Robert P Kimberly10, Susan Manzi14, Michelle A Petri15, Annette Lee16, Peter K Gregersen16, Michael F Seldin4, Lars Rönnblom5, Lindsey A Criswell3, Ann-Christine Syvänen2, Timothy W Behrens1 & Robert R Graham1
Abstract
Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 
10-8): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P
1 10-5. A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 10-3) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
- Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.
- Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
- Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, California, USA.
- Rowe Program in Genetics, University of California at Davis, Davis, California, USA.
- Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
- Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
- Section of Rheumatology, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden.
- Department of Rheumatology, Umeå University Hospital, Umeå, Sweden.
- Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
- University of Alabama at Birmingham, Birmingham, Alabama, USA.
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
- University of Texas–Houston Health Science Center, Houston, Texas, USA.
- University of Puerto Rico Medical Science Campus, San Juan, Puerto Rico.
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
- The Feinstein Institute for Medical Research, North Shore–Long Island Jewish Health System, Manhasset, New York, USA.
Correspondence to: Robert R Graham1 e-mail: graham.robert@gene.com
