出版日期：2024-03-27 00:00:00

著者：Chiang, Pin-hsuan; Tsai, Han-ying; Chang, Yu-jung; Hsieh, Ai-ru

著錄名稱、卷期、頁數：Journal of Advanced Research

摘要：Introduction The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined. Objectives To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP. Methods A meta-analysis comprising 26 case−control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP. Results Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein−protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained. Conclusion With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.

關鍵字：Dry eye disease;Depression;Meta-analysis;Genome-wide association study;Mendelian randomization;Multimodality Biobank

語言：zh_TW

ISSN：2090-1224

期刊性質：國外

收錄於：SCI

通訊作者：Ai-Ru Hsieh(謝璦如), Shih-Hwa Chiou

審稿制度：是

國別：USA

出版型式：電子版