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

A Corrigendum to this article was published on 01 April 2009

This article has been updated

Abstract

Sarcoidosis is a complex chronic inflammatory disorder with predominant manifestation in the lung. In the first genome-wide association study (>440,000 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 × 10−13, rs7091565: P = 1.0 × 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, C > T, 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.

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Figure 1: Significance of disease association and LD structure in the 10q22.3 region.
Figure 2: Expression and localization of ANXA11 in human tissues.
Figure 3: Schematic presentation of the annexin A11 protein.

Change history

  • 24 March 2009

    NOTE: In the version of this article initially published, the SNP rs1049550 listed in the abstract was indicated incorrectly as a T>C change. It is a C>T change. On the third page of the article, the haplotype containing rs1049550 was incorrectly listed as TATACC. It should be AGCATT. These errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

The authors wish to thank all individuals with sarcoidosis, families and physicians for their cooperation. The efforts of the German Sarcoidosis Patients Organization (Deutsche Sarkoidose-Vereinigung) and the contribution of pulmonary specialist physicians are gratefully acknowledged. The authors wish to thank T. Wienker, M. Steffens, M. Albrecht, T. Wesse and C. von der Lanken for expert technical help, R. Kleindorp and G. Richter for logistic help, and R. Vogler for database and computer support. This study was funded by the German National Genome Research Network (NGFN-2).

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S.H. performed the SNP selection, genotyping and data analysis, drafted the manuscript and prepared the tables and parts of the figures; A.Franke and A.Fischer helped with data analysis and contributed to the design and the writing of the manuscript; G.J. and P.R. performed the protein, immunohistochemistry and cDNA experiments and contributed to the manuscript; M.K. supervised the statistical analysis and edited the paper; M.N. performed the haplotype analysis and helped with data analysis; M.S. and J.M.-Q. coordinated the recruitment, collected the phenotype data and contributed to the writing of the manuscript; K.I.G. provided the bronchoalveolar lavage and transbronchial biopsy samples; S.H. and S.S. jointly designed and supervised the experiment and wrote the manuscript.

Corresponding author

Correspondence to Stefan Schreiber.

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Supplementary Methods, Supplementary Tables 1–3, Supplementary Figures 1–4 (PDF 1173 kb)

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Hofmann, S., Franke, A., Fischer, A. et al. Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis. Nat Genet 40, 1103–1106 (2008). https://doi.org/10.1038/ng.198

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