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

ABSTRACT: 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< or = 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.

SUBMITTER: Gateva V 

PROVIDER: S-EPMC2925843 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Gateva Vesela V   Sandling Johanna K JK   Hom Geoff G   Taylor Kimberly E KE   Chung Sharon A SA   Sun Xin X   Ortmann Ward W   Kosoy Roman R   Ferreira Ricardo C RC   Nordmark Gunnel G   Gunnarsson Iva I   Svenungsson Elisabet E   Padyukov Leonid L   Sturfelt Gunnar G   Jönsen Andreas A   Bengtsson Anders A AA   Rantapää-Dahlqvist Solbritt S   Baechler Emily C EC   Brown Elizabeth E EE   Alarcón Graciela S GS   Edberg Jeffrey C JC   Ramsey-Goldman Rosalind R   McGwin Gerald G   Reveille John D JD   Vilá Luis M LM   Kimberly Robert P RP   Manzi Susan S   Petri Michelle A MA   Lee Annette A   Gregersen Peter K PK   Seldin Michael F MF   Rönnblom Lars L   Criswell Lindsey A LA   Syvänen Ann-Christine AC   Behrens Timothy W TW   Graham Robert R RR  

Nature genetics 20091018 11

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), J  ...[more]