TY - JOUR
T1 - A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
AU - Gateva, Vesela
AU - Sandling, Johanna K.
AU - Hom, Geoff
AU - Taylor, Kimberly E.
AU - Chung, Sharon A.
AU - Sun, Xin
AU - Ortmann, Ward
AU - Kosoy, Roman
AU - Ferreira, Ricardo C.
AU - Nordmark, Gunnel
AU - Gunnarsson, Iva
AU - Svenungsson, Elisabet
AU - Padyukov, Leonid
AU - Sturfelt, Gunnar
AU - Jönsen, Andreas
AU - Bengtsson, Anders A.
AU - Rantapää-Dahlqvist, Solbritt
AU - Baechler, Emily C.
AU - Brown, Elizabeth E.
AU - Alarcón, Graciela S.
AU - Edberg, Jeffrey C.
AU - Ramsey-Goldman, Rosalind
AU - McGwin, Gerald
AU - Reveille, John D.
AU - Vilá, Luis M.
AU - Kimberly, Robert P.
AU - Manzi, Susan
AU - Petri, Michelle A.
AU - Lee, Annette
AU - Gregersen, Peter K.
AU - Seldin, Michael F.
AU - Rönnblom, Lars
AU - Criswell, Lindsey A.
AU - Syvänen, Ann Christine
AU - Behrens, Timothy W.
AU - Graham, Robert R.
N1 - Funding Information:
We thank the many affected individuals and physicians who contributed DNA samples and clinical data for this study; M.I. Kamboh and P. Davies for the use of Alzheimer’s disease samples as controls in our study; B. Neale for assistance in the percent of genetic variance explained calculation; and S. Sanna and C. Willer for assistance in generating regional association plots. Genotyping of the Swedish samples by the 12K chips was performed using equipment of the SNP technology platform in Uppsala. We thank C. Enström and A.-C. Wiman for assistance with genotyping. Financial support was obtained from the Swedish Research Council for Medicine, the Knut and Alice Wallenberg Foundation the Swedish Rheumatism Association, the King Gustaf V 80th Birthday Foundation, COMBINE, and a Target Identification in Lupus (TIL) grant from the Alliance for Lupus Research, US. This work was supported in part by R01 AR44804, K24 AR02175, the Mary Kirkland Center for Lupus Research, RO1 AR43727 and Institute for Clinical and Translational Research UL1RR025005. These studies were performed in part in the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco, with funds provided by the National Center for Research Resources, 5 M01 RR-00079, US Public Health Service.
PY - 2009/11
Y1 - 2009/11
N2 - 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 × 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 × 10 5. A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P 1 × 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.
AB - 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 × 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 × 10 5. A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P 1 × 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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U2 - 10.1038/ng.468
DO - 10.1038/ng.468
M3 - Article
C2 - 19838195
AN - SCOPUS:70350650472
SN - 1061-4036
VL - 41
SP - 1228
EP - 1233
JO - Nature genetics
JF - Nature genetics
IS - 11
ER -