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Fischer, A.* ; Schmid, B.* ; Ellinghaus, D.* ; Nothnagel, M.* ; Gaede, K.I.* ; Schürmann, M.* ; Lipinski, S.* ; Rosenstiel, P.* ; Zissel, G.* ; Höhne, K.* ; Petrek, M.* ; Kolek, V.* ; Pabst, S.* ; Grohe, C.* ; Grunewald, J.* ; Ronninger, M.* ; Eklund, A.* ; Padyukov, L.* ; Gieger, C. ; Wichmann, H.-E. ; Nebel, A.* ; Franke, A.* ; Müller-Quernheim, J.* ; Hofmann, S.* ; Schreiber, S.*

A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1.

Am. J. Respir. Crit. Care Med. 186, 877-885 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Rationale: Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Among others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known. Objectives: To identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genomewide association scan for these phenotypes. Methods: After quality control, the genome-wide association scan comprised nearly 1.3 million imputed single-nucleotide polymorphisms based on an Affymetrix 6.0 Gene Chip dataset of 564 German sarcoidosis cases, including 176 acute and 354 chronic cases and 1,575 control subjects. Measurements and Main Results: We identified chromosome 11q13.1 (rs479777) as a novel locus influencing susceptibility to sarcoidosis with genome-wide significance. The marker was significantly associated in three distinct German case-control populations and in an additional German family sample with odds ratios ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (odds ratio, 0.75) and from Sweden (odds ratio, 0.79). In a meta-analysis of the included European case-control samples the marker yielded a P value of 2.68 x 10(-18). The locus was previously reported to be associated with Crohn disease, psoriasis, alopecia areata, and leprosy. For sarcoidosis, fine-mapping and expression analysis suggest KCNK4, PRDX5, PCLB3, and most promising CCDC88B as candidates for the underlying risk gene in the associated region. Conclusions: This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn disease and psoriasis.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Sarcoidosis ; Genome-wide Association Study ; Imputation ; Gipie ; Prdx5; Genome-wide Association ; Beta Gene Polymorphisms ; Susceptibility Loci ; Lofgrens-syndrome ; Btnl2 Gene ; Disease ; Anxa11 ; Visualization ; Expression ; Database
ISSN (print) / ISBN 1073-449X
e-ISSN 1535-4970
Journal American Journal of Respiratory and Critical Care Medicine
Quellenangaben Volume: 186, Issue: 9, Pages: 877-885 Article Number: , Supplement: ,
Publisher American Thoracic Society
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)