Journal
NATURE GENETICS
Volume 41, Issue 11, Pages 1228-U93Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.468
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Funding
- NCRR NIH HHS [5 M01 RR-00079, UL1 RR025741, UL1 RR025005, UL1RR025005, M01 RR000079, UL1 RR025005-01] Funding Source: Medline
- NIAMS NIH HHS [R01 AR44804, K24 AR02175, K24 AR002175-01A1, K24 AR002175, R01 AR43727, R01 AR043727-03, R01 AR044804-01A1, R01 AR043727] Funding Source: Medline
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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.
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