Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci by International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley John B, Alarcón-Riquelme Marta E, Criswell Lindsey A, Jacob Chaim O, Kimberly Robert P, Moser Kathy L, Tsao Betty P, Vyse Timothy J, Langefeld Carl D, Nath Swapan K, Guthridge Joel M, Cobb Beth L, Mirel Daniel B, Marion Miranda C, Williams Adrienne H, Divers Jasmin, Wang Wei, Frank Summer G, Namjou Bahram, Gabriel Stacey B, Lee Annette T, Gregersen Peter K, Behrens Timothy W, Taylor Kimberly E, Fernando Michelle, Zidovetzki Raphael, Gaffney Patrick M, Edberg Jeffrey C, Rioux John D, Ojwang Joshua O, James Judith A, Merrill Joan T, Gilkeson Gary S, Seldin Michael F, Yin Hong, Baechler Emily C, Li Quan-Zhen, Wakeland Edward K, Bruner Gail R, Kaufman Kenneth M, Kelly Jennifer A in Nature genetics (2008).

[PMID: 18204446] PubMed


Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). 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 x 10(-7) < P(overall) < 1.6 x 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 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

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