Letter abstract

Nature Genetics 40, 204 - 210 (2008)
Published online: 20 January 2008 | doi:10.1038/ng.81

Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci

The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN)11, John B Harley1,2, Marta E Alarcón-Riquelme3, Lindsey A Criswell4, Chaim O Jacob5, Robert P Kimberly6, Kathy L Moser1,7, Betty P Tsao8, Timothy J Vyse9 & Carl D Langefeld10


Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambdaS = approx30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 times 10-7 < Poverall < 1.6 times 10-23; odds ratio = 0.82–1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 times 10-5) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at greater than or equal to9 other loci (P < 2 times 10-7). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

  1. Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104, USA.
  2. US Department of Veterans Affairs Medical Center, 921 NE 13th Street, Oklahoma City, Oklahoma 73104, USA, and University of Oklahoma Health Sciences Center, 1100 N Lindsey, Oklahoma City, Oklahoma 73104, USA.
  3. University of Uppsala, Olofsgatan St 10B, Uppsala SE-751 05 Sweden.
  4. University of California at San Francisco, 374 Parnassus Ave, San Francisco, California 94143, USA.
  5. University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
  6. University of Alabama at Birmingham, 1900 University Blvd., Birmingham, Alabama 35294, USA.
  7. University of Minnesota, 312 Church Street, Minneapolis, Minnesota 55455, USA.
  8. University of California at Los Angeles, 1000 Veterans Avenue, Los Angeles, California 90095, USA.
  9. Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN UK.
  10. Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, North Carolina 27157, USA.
  11. SLEGEN members are listed above; other contributing authors are listed at the end of the paper.
  12. Broad Institute, 7 Cambridge Center, Boston, Massachusetts 02142 USA.
  13. Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, New York 11030, USA.
  14. Genentech, Inc.,1 DNA Way, South San Francisco, California 94080, USA.
  15. University of California at Riverside, 900 University Avenue, Riverside, California 92521, USA.
  16. Université de Montréal, 5000 rue Belanger, Montréal H1T 1C8, Canada.
  17. Medical University of South Carolina, 135 Rutledge Avenue, Charleston, South Carolina 29403, USA.
  18. University of California at Davis, 1 Shields Avenue, Davis, California 95616, USA.
  19. University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas 75235, USA.

Correspondence to: John B Harley1,2Carl D Langefeld10 e-mail: SLEGEN@wfubmc.edu