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

Vesela Gateva; Johanna K. Sandling; Geoff Hom; Kimberly E. Taylor; Sharon A. Chung; Xin Sun; Ward Ortmann; Roman Kosoy; Ricardo C. Ferreira; Gunnel Nordmark; Iva Gunnarsson; Elisabet Svenungsson; Leonid Padyukov; Gunnar Sturfelt; Andreas Jönsen; Anders A. Bengtsson; Solbritt Rantapää-Dahlqvist; Emily C. Baechler; Elizabeth E. Brown; Graciela S. Alarcón; Jeffrey C. Edberg; Rosalind Ramsey-Goldman; Gerald McGwin; John D. Reveille; Luis M. Vilá; Robert P. Kimberly; Susan Manzi; Michelle A. Petri; Annette Lee; Peter K. Gregersen; Michael F. Seldin; Lars Rönnblom; Lindsey A. Criswell; Ann Christine Syvänen; Timothy W. Behrens; Robert R. Graham

doi:10.1038/ng.468

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

Vesela Gateva, Johanna K. Sandling, Geoff Hom, Kimberly E. Taylor, Sharon A. Chung, Xin Sun, Ward Ortmann, Roman Kosoy, Ricardo C. Ferreira, Gunnel Nordmark, Iva Gunnarsson, Elisabet Svenungsson, Leonid Padyukov, Gunnar Sturfelt, Andreas Jönsen, Anders A. Bengtsson, Solbritt Rantapää-Dahlqvist, Emily C. Baechler, Elizabeth E. Brown, Graciela S. AlarcónJeffrey C. Edberg, Rosalind Ramsey-Goldman, Gerald McGwin, John D. Reveille, Luis M. Vilá, Robert P. Kimberly, Susan Manzi, Michelle A. Petri, Annette Lee, Peter K. Gregersen, Michael F. Seldin, Lars Rönnblom, Lindsey A. Criswell, Ann Christine Syvänen, Timothy W. Behrens, Robert R. Graham

Medicine - Rheumatic and Autoimmune

Research output: Contribution to journal › Article › peer-review

685 Scopus citations

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 × 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.

Original language	English (US)
Pages (from-to)	1228-1233
Number of pages	6
Journal	Nature Genetics
Volume	41
Issue number	11
DOIs	https://doi.org/10.1038/ng.468
State	Published - Nov 2009

Bibliographical note

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.

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Gateva, V., Sandling, J. K., Hom, G., Taylor, K. E., Chung, S. A., Sun, X., Ortmann, W., Kosoy, R., Ferreira, R. C., Nordmark, G., Gunnarsson, I., Svenungsson, E., Padyukov, L., Sturfelt, G., Jönsen, A., Bengtsson, A. A., Rantapää-Dahlqvist, S., Baechler, E. C., Brown, E. E., ... Graham, R. R. (2009). A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nature Genetics, 41(11), 1228-1233. https://doi.org/10.1038/ng.468

Gateva, V, Sandling, JK, Hom, G, Taylor, KE, Chung, SA, Sun, X, Ortmann, W, Kosoy, R, Ferreira, RC, Nordmark, G, Gunnarsson, I, Svenungsson, E, Padyukov, L, Sturfelt, G, Jönsen, A, Bengtsson, AA, Rantapää-Dahlqvist, S, Baechler, EC, Brown, EE, Alarcón, GS, Edberg, JC, Ramsey-Goldman, R, McGwin, G, Reveille, JD, Vilá, LM, Kimberly, RP, Manzi, S, Petri, MA, Lee, A, Gregersen, PK, Seldin, MF, Rönnblom, L, Criswell, LA, Syvänen, AC, Behrens, TW & Graham, RR 2009, 'A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus', Nature Genetics, vol. 41, no. 11, pp. 1228-1233. https://doi.org/10.1038/ng.468

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title = "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 × 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.",

author = "Vesela Gateva and Sandling, {Johanna K.} and Geoff Hom and Taylor, {Kimberly E.} and Chung, {Sharon A.} and Xin Sun and Ward Ortmann and Roman Kosoy and Ferreira, {Ricardo C.} and Gunnel Nordmark and Iva Gunnarsson and Elisabet Svenungsson and Leonid Padyukov and Gunnar Sturfelt and Andreas J{\"o}nsen and Bengtsson, {Anders A.} and Solbritt Rantap{\"a}{\"a}-Dahlqvist and Baechler, {Emily C.} and Brown, {Elizabeth E.} and Alarc{\'o}n, {Graciela S.} and Edberg, {Jeffrey C.} and Rosalind Ramsey-Goldman and Gerald McGwin and Reveille, {John D.} and Vil{\'a}, {Luis M.} and Kimberly, {Robert P.} and Susan Manzi and Petri, {Michelle A.} and Annette Lee and Gregersen, {Peter K.} and Seldin, {Michael F.} and Lars R{\"o}nnblom and Criswell, {Lindsey A.} and Syv{\"a}nen, {Ann Christine} and Behrens, {Timothy W.} and Graham, {Robert R.}",

note = "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{\textquoteright}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. Enstr{\"o}m 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.",

year = "2009",

month = nov,

doi = "10.1038/ng.468",

language = "English (US)",

volume = "41",

pages = "1228--1233",

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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.

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

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Bibliographical note

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