Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

• DOI: 10.1371/journal.pgen.1000084
• Publication Date: 2008-05-29T22:31:12Z
• Authors: Kimberly E. Taylor; Elaine F. Remmers; Annette T. Lee; Ward A. Ortmann; Robert M. Plenge; Chao Tian; Sharon A. Chung; Joanne Nititham; Geoffrey Hom; Amy H. Kao; F. Yesim Demirci; M. Ilyas Kamboh; Michelle Petri; Susan Manzi; Daniel L. Kastner; Michael F. Seldin; Peter K. Gregersen; Timothy W. Behrens; Lindsey A. Criswell
• Keywords: SNP; Genome-wide Association Study; Genetic Association

Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as risk factor for SLE, but relationship specific SLE subphenotypes not studied. We studied 137 SNPs region genotyped 4 independent case series (total n = 1398) and 2560 healthy controls, along data cases. Using conditional testing, we confirmed most significant haplotype risk. then SNP marking this association subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, age at diagnosis. To prevent possible type-I errors from population stratification, reanalyzed using subset of subjects determined to be homogeneous based on principal components analysis genome-wide data. that four very high LD (r2 0.94 0.99) were strongly associated there was no compelling evidence additional loci region. rs7574865 had minor allele frequency (MAF) 31.1% cases compared 22.5% controls (OR 1.56, p 10−16). This more characterized by double-stranded DNA autoantibodies (MAF 35.1%, OR 1.86, p<10−19), nephritis 34.3%, 1.80, p<10−11), diagnosis<30 years 33.8%, 1.77, p<10−13). An severe even striking 39.2%, 2.35, p<10−4 subjects). In contrast, less oral ulcers, manifestation milder disease. conclude common contributes phenotypic heterogeneity predisposing specifically