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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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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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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