Genotype-Phenotype Relationship in Sarcoidosis
Final Report Abstract
Within the reported project, the European GenPhenReSa consortium recruited over 2000 sarcoidosis patients with extraordinary phenotyping depth, which adequately reflects the heterogeneous nature of the disease. With great efforts, homogenous recruitment and phenotyping procedures were established and phenotyping was quality controlled in an exceedingly large proportion of cases (>45%), while unexpected drop-outs were compensated by the involvement of additional recruitment centers. Analyses of the phenotype data point to a yet unknown co-occurrence of sarcoidosis phenotypes with regards to affected organs and symptoms: This finding might be of value in clinical application by supporting the identification of high-risk patients. According to the work plan, DNA of the patients was isolated and genotyped for selected genetic variants, in order to identify markers that distinguish certain subphenotypes, such as a resolving or persistent course of the disease or specific organ involvement. Several markers were identified that are significantly associated with a certain course of the disease. However, the predictive value of the markers was too low for clinical application, which is in line with recent findings for other complex diseases. Predicting complex phenotypes from genetic data is now realized to be challenging and demands the analysis of whole-genome data of deeply phenotyped patient collections, such as the GenPhenReSa cohort. As such, this sample will be of great value beyond this project.
Publications
- A genome-wide association study reveals evidence of association with sarcoidosis at 6p12.1. Eur Respr J 2011;38:1127-1135
Hofmann S, Fischer A, Till A, Müller-Quernheim J, Häsler R, Franke A, Gäde Kl, Schaarschmidt H, Rosenstiel P, Nebel A, Schürmann M, Nothnagel M, Schreiber S; GenPhenReSa Consortium
(See online at https://doi.org/10.1183/09031936.00001711)
