دورية أكاديمية
A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1.
| العنوان: | A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1. |
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| المؤلفون: | 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. |
| المصدر: | Am. J. Respir. Crit. Care Med. 186, 877-885 (2012) |
| بيانات النشر: | American Thoracic Society |
| سنة النشر: | 2012 |
| المجموعة: | PuSH - Publikationsserver des Helmholtz Zentrums München |
| مصطلحات موضوعية: | Sarcoidosis, Genome-wide Association Study, Imputation, Gipie, Prdx5 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1073-449X 1535-4970 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/22837380; info:eu-repo/semantics/altIdentifier/wos/WOS:000311128300014; info:eu-repo/semantics/altIdentifier/isbn/1073-449X; info:eu-repo/semantics; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=11490Test; urn:isbn:1073-449X; urn:issn:1073-449X; urn:issn:1535-4970 |
| DOI: | 10.1164/rccm.201204-0708OC |
| الإتاحة: | https://doi.org/10.1164/rccm.201204-0708OCTest https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=11490Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.A8BA6B73 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1073449X 15354970 |
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| DOI: | 10.1164/rccm.201204-0708OC |