Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis

被引：184

作者：

Hofmann, Sylvia ^{[1
]}

Franke, Andre ^{[1
]}

Fischer, Annegret ^{[1
]}

Jacobs, Gunnar ^{[1
]}

Nothnagel, Michael ^{[2
]}

Gaede, Karoline I. ^{[3
]}

Schuermann, Manfred ^{[4
]}

Mueller-Quernheim, Joachim ^{[5
]}

Krawczak, Michael ^{[2
]}

Rosenstiel, Philip ^{[1
]}

Schreiber, Stefan ^{[1
,6
]}

机构：

[1] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany

[2] Univ Kiel, Inst Med Informat & Stat, D-24105 Kiel, Germany

[3] Res Ctr Borstel, D-23845 Borstel, Germany

[4] Med Univ Lubeck, Inst Human Genet, D-23538 Lubeck, Germany

[5] Univ Freiburg, Dept Pneumol, D-79106 Freiburg, Germany

[6] Univ Kiel, Dept Internal Med, D-24105 Kiel, Germany

来源：

NATURE GENETICS | 2008年 / 40卷 / 09期

关键词：

D O I：

10.1038/ng.198

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Sarcoidosis is a complex chronic inflammatory disorder with predominant manifestation in the lung. In the first genome-wide association study (4440,000 SNPs) of this disease, comprising 499 German individuals with sarcoidosis and 490 controls, we detected a series of genetic associations. The strongest association signal maps to the ANXA11 (annexin A11) gene on chromosome 10q22.3. Validation in an independent sample (1,649 cases, 1,832 controls) confirmed the association (SNP rs2789679: P = 3.0 x 10(-13), rs7091565: P = 1.0 x 10(-5), allele-based test). Extensive fine mapping located the association signal to a region between exon 5 and exon 14 of ANXA11. A common nonsynonymous SNP (rs1049550, T > C, R230C) was found to be strongly associated with sarcoidosis. The GWAS lead SNP and additional risk variants in the region (rs1953600, rs2573346, rs2784773) were in strong linkage disequilibrium with rs1049550. Annexin A11 has complex and essential functions in several biological pathways, including apoptosis and proliferation.

引用

页码：1103 / 1106

页数：4

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