{"title":"Deciphering the genetic interplay between depression and dysmenorrhea: a Mendelian randomization study.","authors":"Shuhe Liu, Zhen Wei, Daniel F Carr, John Moraros","doi":"10.1093/bib/bbae589","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study aims to explore the link between depression and dysmenorrhea by using an integrated and innovative approach that combines genomic, transcriptomic, and protein interaction data/information from various resources.</p><p><strong>Methods: </strong>A two-sample, bidirectional, and multivariate Mendelian randomization (MR) approach was applied to determine causality between dysmenorrhea and depression. Genome-wide association study (GWAS) data were used to identify genetic variants associated with both dysmenorrhea and depression, followed by colocalization analysis of shared genetic influences. Expression quantitative trait locus (eQTL) data were analyzed from public databases to pinpoint target genes in relevant tissues. Additionally, a protein-protein interaction (PPI) network was constructed using the STRING database to analyze interactions among identified proteins.</p><p><strong>Results: </strong>MR analysis confirmed a significant causal effect of depression on dysmenorrhea ['odds ratio' (95% confidence interval) = 1.51 (1.19, 1.91), P = 7.26 × 10-4]. Conversely, no evidence was found to support a causal effect of dysmenorrhea on depression (P = .74). Genetic analysis, using GWAS and eQTL data, identified single-nucleotide polymorphisms in several genes, including GRK4, TRAIP, and RNF123, indicating that depression may impact reproductive function through these genetic pathways, with a detailed picture presented by way of analysis in the PPI network. Colocalization analysis highlighted rs34341246(RBMS3) as a potential shared causal variant.</p><p><strong>Conclusions: </strong>This study suggests that depression significantly affects dysmenorrhea and identifies key genes and proteins involved in this interaction. The findings underline the need for integrated clinical and public health approaches that screen for depression among women presenting with dysmenorrhea and suggest new targeted preventive strategies.</p>","PeriodicalId":9209,"journal":{"name":"Briefings in bioinformatics","volume":"26 1","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11596086/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Briefings in bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/bib/bbae589","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: This study aims to explore the link between depression and dysmenorrhea by using an integrated and innovative approach that combines genomic, transcriptomic, and protein interaction data/information from various resources.
Methods: A two-sample, bidirectional, and multivariate Mendelian randomization (MR) approach was applied to determine causality between dysmenorrhea and depression. Genome-wide association study (GWAS) data were used to identify genetic variants associated with both dysmenorrhea and depression, followed by colocalization analysis of shared genetic influences. Expression quantitative trait locus (eQTL) data were analyzed from public databases to pinpoint target genes in relevant tissues. Additionally, a protein-protein interaction (PPI) network was constructed using the STRING database to analyze interactions among identified proteins.
Results: MR analysis confirmed a significant causal effect of depression on dysmenorrhea ['odds ratio' (95% confidence interval) = 1.51 (1.19, 1.91), P = 7.26 × 10-4]. Conversely, no evidence was found to support a causal effect of dysmenorrhea on depression (P = .74). Genetic analysis, using GWAS and eQTL data, identified single-nucleotide polymorphisms in several genes, including GRK4, TRAIP, and RNF123, indicating that depression may impact reproductive function through these genetic pathways, with a detailed picture presented by way of analysis in the PPI network. Colocalization analysis highlighted rs34341246(RBMS3) as a potential shared causal variant.
Conclusions: This study suggests that depression significantly affects dysmenorrhea and identifies key genes and proteins involved in this interaction. The findings underline the need for integrated clinical and public health approaches that screen for depression among women presenting with dysmenorrhea and suggest new targeted preventive strategies.
期刊介绍:
Briefings in Bioinformatics is an international journal serving as a platform for researchers and educators in the life sciences. It also appeals to mathematicians, statisticians, and computer scientists applying their expertise to biological challenges. The journal focuses on reviews tailored for users of databases and analytical tools in contemporary genetics, molecular and systems biology. It stands out by offering practical assistance and guidance to non-specialists in computerized methodologies. Covering a wide range from introductory concepts to specific protocols and analyses, the papers address bacterial, plant, fungal, animal, and human data.
The journal's detailed subject areas include genetic studies of phenotypes and genotypes, mapping, DNA sequencing, expression profiling, gene expression studies, microarrays, alignment methods, protein profiles and HMMs, lipids, metabolic and signaling pathways, structure determination and function prediction, phylogenetic studies, and education and training.