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

被引：699

作者：

Gateva, Vesela ^{[1
]}

Sandling, Johanna K.

Hom, Geoff ^{[1
]}

Taylor, Kimberly E. ^{[3
]}

Chung, Sharon A. ^{[3
]}

Sun, Xin ^{[1
]}

Ortmann, Ward ^{[1
]}

Kosoy, Roman ^{[4
]}

Ferreira, Ricardo C. ^{[1
]}

Nordmark, Gunnel ^{[2
]}

Gunnarsson, Iva ^{[5
]}

Svenungsson, Elisabet ^{[5
]}

Padyukov, Leonid ^{[5
]}

Sturfelt, Gunnar ^{[6
]}

Jonsen, Andreas ^{[6
]}

Bengtsson, Anders A. ^{[6
]}

Rantapaa-Dahlqvist, Solbritt ^{[7
]}

Baechler, Emily C. ^{[8
]}

Brown, Elizabeth E. ^{[9
]}

Alarcon, Graciela S. ^{[9
]}

Edberg, Jeffrey C. ^{[9
]}

Ramsey-Goldman, Rosalind ^{[10
]}

McGwin, Gerald, Jr. ^{[9
]}

Reveille, John D. ^{[11
]}

Vila, Luis M. ^{[12
]}

Kimberly, Robert P. ^{[9
]}

Manzi, Susan ^{[13
]}

Petri, Michelle A. ^{[14
]}

Lee, Annette ^{[15
]}

Gregersen, Peter K. ^{[15
]}

Seldin, Michael F. ^{[4
]}

Ronnblom, Lars ^{[2
]}

Criswell, Lindsey A. ^{[3
]}

Syvanen, Ann-Christine

Behrens, Timothy W. ^{[1
]}

Graham, Robert R. ^{[1
]}

机构：

[1] Genentech Inc, Immunol Biomarkers Grp, San Francisco, CA 94080 USA

[2] Uppsala Univ, Dept Med Sci, Rheumatol Sect, Uppsala, Sweden

[3] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA

[4] Univ Calif Davis, Rowe Program Genet, Davis, CA 95616 USA

[5] Karolinska Univ Hosp, Dept Med, Karolinska Inst, Rheumatol Unit, Stockholm, Sweden

[6] Univ Lund Hosp, Dept Clin Sci, Rheumatol Sect, S-22185 Lund, Sweden

[7] Umea Univ Hosp, Dept Rheumatol, S-90185 Umea, Sweden

[8] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA

[9] Univ Alabama Birmingham, Birmingham, AL USA

[10] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[11] Univ Texas Houston Hlth Sci Ctr, Houston, TX USA

[12] Univ Puerto Rico, San Juan, PR 00936 USA

[13] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA

[14] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[15] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 11期

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; GENETIC-VARIANTS; COMMON VARIANTS; POLYMORPHISMS; MULTIPLE; PATHOGENESIS; METAANALYSIS; CLEC16A; LINKAGE;

D O I：

10.1038/ng.468

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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.

引用

页码：1228 / U93

页数：8

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