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

Annegret Fischer, Benjamin Schmid, David Ellinghaus, Michael Nothnagel, Karoline I. Gaede, Manfred Schürmann, Simone Lipinski, Philip Rosenstiel, Gernot Zissel, Kerstin Höhne, Martin Petrek, Vitezslav Kolek, Stefan Pabst, Christian Grohé, Johan Grunewald, Marcus Ronninger, Anders Eklund, Leonid Padyukov, Christian Gieger, H. Erich WichmannAlmut Nebel, Andre Franke, Joachim Müller-Quernheim, Sylvia Hofmann, Stefan Schreiber*

*Corresponding author for this work
27 Citations (Scopus)


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 3 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 sharedby sarcoidosis, Crohndisease and psoriasis.

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number9
Pages (from-to)877-885
Number of pages9
Publication statusPublished - 01.11.2012


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