Integrative genomic and transcriptomic analysis of genetic markers in Dupuytren’s disease

• Main Authors: Junghyun Jung, Go Woon Kim, Byungjo Lee, Jong Wha J. Joo, Wonhee Jang
• Format: Article
• Language: English
• Published: BMC 2019-07-01
• Series: BMC Medical Genomics
• Subjects: Dupuytren’s disease; Unfolded protein response (UPR); Endoplasmic reticulum (ER) stress; Multiple-phenotype analysis; trans-regulatory hotspots; ZFP57 zinc finger protein
• Online Access: http://link.springer.com/article/10.1186/s12920-019-0518-3

Abstract Background Dupuytren’s disease (DD) is a fibroproliferative disorder characterized by thickening and contracting palmar fascia. The exact pathogenesis of DD remains unknown. Results In this study, we identified co-expressed gene set (DD signature) consisting of 753 genes via weighted gene co-expression network analysis. To confirm the robustness of DD signature, module enrichment analysis and meta-analysis were performed. Moreover, this signature effectively classified DD disease samples. The DD signature were significantly enriched in unfolded protein response (UPR) related to endoplasmic reticulum (ER) stress. Next, we conducted multiple-phenotype regression analysis to identify trans-regulatory hotspots regulating expression levels of DD signature using Genotype-Tissue Expression data. Finally, 10 trans-regulatory hotspots and 16 eGenes genes that are significantly associated with at least one cis-eQTL were identified. Conclusions Among these eGenes, major histocompatibility complex class II genes and ZFP57 zinc finger protein were closely related to ER stress and UPR, suggesting that these genetic markers might be potential therapeutic targets for DD.