A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus

作者：Gateva Vesela; Sandling Johanna K; Hom Geoff; Taylor Kimberly E; Chung Sharon A; Sun Xin; Ortmann Ward; Kosoy Roman; Ferreira Ricardo C; Nordmark Gunnel; Gunnarsson Iva; Svenungsson Elisabet; Padyukov Leonid; Sturfelt Gunnar; Jonsen Andreas; Bengtsson Anders A; Rantapaa Dahlqvist Solbritt; Baechler Emily C; Brown Elizabeth E; Alarcon Graciela S; Edberg Jeffrey C; Ramsey Goldman Rosalind; McGwin Gerald Jr; Reveille John D; Vila Luis M; Kimberly Robert P

来源：Nature Genetics, 2009, 41(11): 1228-U93.

DOI：10.1038/ng.468

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 x 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 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 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.

• 出版日期2009-11
• 单位河北医科大学; 西北大学