title: Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis.
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 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, C > T, [corrected] 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.
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel D-24105, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hofmann
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Annegret
authors.initials: A
authors.lastname: Fischer
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobs
authors.forename: Michael
authors.initials: M
authors.lastname: Nothnagel
authors.forename: Karoline I
authors.initials: KI
authors.lastname: Gaede
authors.forename: Manfred
authors.initials: M
authors.lastname: Schürmann
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000595:Amino Acid Sequence; D017302:Annexins / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D012507:Sarcoidosis / Q000235:genetics*; D020539:Sequence Analysis, Protein; D054928:Validation Studies as Topic
chemical_list: D017302:Annexins