A Novel Sarcoidosis Risk Locus for Europeans on Chromosome 11q13.1
Annegret Fischer1,
Benjamin Schmid2,
David Ellinghaus3,
Michael Nothnagel4,
Karoline I Gaede5,
Manfred Schürmann6,
Simone Lipinski7,
Philip Rosenstiel8,
Gernot Zissel9,
Kerstin Höhne10,
Martin Petrek11,
Vitezslav Kolek12,
Stefan Pabst13,
Christian Grohé14,
Johan Grunewald15,
Marcus Ronninger16,
Anders Eklund17,
Leonid Padyukov18,
Christian Gieger19,
H.-Erich Wichmann20,
Almut Nebel21,
Andre Franke22,
Joachim Müller-Quernheim23,
Sylvia Hofmann24 and
Stefan Schreiber25⇓
+ Author Affiliations
1Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
2Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
3Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
4Institute of Medical Informatics and Statistics, Christian-Albrechts University, Kiel, Germany
5Department of Pneumology, Research Center Borstel, Borstel, Germany
6Institute of Human Genetics, University of Lübeck, Lübeck, Germany
7Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
8Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
9Department of Pneumology, University of Freiburg, Freiburg, Germany
10Department of Pneumology, University of Freiburg, Freiburg, Germany
11Laboratory of Immunogenetics and Immunoproteomics, Palacky University Olomouc, Olomouc, Czech Republic
12Department of Respiratory Medicine, Palacky University Olomouc, Olomouc, Czech Republic
13Department of Pneumology, University of Bonn, Bonn, Germany
14Department of Respiratory Medicine, Evangelische Lungenklinik Berlin-Buch, Berlin, Germany
15Department of Medicine, Karolinska Institutet, Stockholm, Sweden
16Department of Medicine, Karolinska Institutet, Stockholm, Sweden
17Department of Medicine, Karolinska Institutet, Stockholm, Sweden
18Department of Medicine, Karolinska Institutet, Stockholm, Sweden
19Institute of Genetic Epidemiology, German Research Center for Environmental Health, Neuherberg, Germany
20Institute of Medical Informatics, Ludwig-Maximilians University, Munich, Germany
21Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
22Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
23Department of Pneumology, University of Freiburg, Freiburg, Germany
24Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
25Institute of Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
Correspondence: Stefan Schreiber, Email: s.schreiber@mucosa.de
Abstract
Rationale: Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Amongst others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known. Objectives: In order to identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genome-wide association scan (GWAS) for these phenotypes. Methods: After quality control, the GWAS 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 1575 controls. 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 ORs ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (OR = 0.75) and from Sweden (OR = 0.79). In a meta-analysis of the included European case-control samples the marker yielded a p value of 2.68x10-18. The locus was previously reported to be associated with Crohn´s disease, alopecia areata, leprosy and psoriasis. 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. Conclusion: 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´s disease and psoriasis.
Received April 18, 2012.
Revision received July 5, 2012.
Accepted July 5, 2012.
european sarcoidosis gene discovered
Moderators: Mike Bartolatz, kwork
-
- Posts: 6595
- Joined: Fri Feb 06, 2004 9:58 pm
european sarcoidosis gene discovered
Mike Bartolatz
Moderator
Moderator