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Am J Respir Crit Care Med. 2012 Nov 1;186(9):877-85. doi: 10.1164/rccm.201204-0708OC. Epub 2012 Jul 26.

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

Author information

1
Christian-Albrechts University, Institute of Clinical Molecular Biology, Schittenhelmstrasse 12, Kiel, Germany. s.schreiber@mucosa.de

Abstract

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 genome-wide 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 × 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.

PMID:
22837380
DOI:
10.1164/rccm.201204-0708OC
[Indexed for MEDLINE]

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