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Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis
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Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis
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Journal Article
Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis
2008
Overview
Stefan Schreiber and colleagues report the results of a genome-wide association study for sarcoidosis, a complex chronic inflammatory disorder. Variants near
ANXA11
and
PLAC9
are associated with elevated risk of the disease, with
ANXA11
as the stronger candidate.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Fundamental and applied biological sciences. Psychology
/ Genetic Predisposition to Disease
/ Genetics
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genome-Wide Association Study
/ Humans
/ letter
/ Polymorphism, Single Nucleotide
