BMC Medical Genomics最新文献

{"title":"Association of the pri-miR-34b/c rs4938723 T > C polymorphism with hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study.","authors":"Wenli Zhang, Jinhong Zhu, Jun Bian, Chunlei Zhou, Shouhua Zhang, Shaohua He, Hongting Lu, Yizhen Wang, Jing He","doi":"10.1186/s12920-025-02179-4","DOIUrl":"10.1186/s12920-025-02179-4","url":null,"abstract":"<p><strong>Background: </strong>Hepatoblastoma is the most prevalent liver cancer affecting children, and its intricate causes are closely linked to genetic variations. This study interrogated the influence of the miR-34b/c rs4938723 T > C polymorphism in hepatoblastoma predisposition in a Han Chinese children study population, comprising 193 cases and 773 controls from East China.</p><p><strong>Methods: </strong>Genotyping was performed via the TaqMan technique. The association between this genetic variant and hepatoblastoma susceptibility was determined via logistic regression models adjusted for age and sex.</p><p><strong>Results: </strong>Our results show that the TC genotype of the miR-34b/c rs4938723 polymorphism is associated with a significantly reduced risk of hepatoblastoma under a heterozygous model (adjusted OR = 0.59, 95% CI = 0.41-0.84, P = 0.003), whereas the CC genotype is associated with an increased risk under a recessive model (adjusted OR = 1.79, 95% CI = 1.17-2.73, P = 0.008). Further stratified analysis revealed that the TC/CC genotypes were linked to a lower risk of hepatoblastoma in girls and those with advanced clinical stages (III + IV). Furthermore, we identified the miR-34b/c rs4938723 polymorphism as an expression quantitative trait locus that affects the expression of nearby genes. The CC genotype was related to a decrease in LAYN expression in the colon, brain, and lung and decreased PPP2R1B expression in the testis. These findings suggest that miR-34b/c rs4938723 T > C has the potential to modify hepatoblastoma predisposition through its regulatory effects on gene expression.</p><p><strong>Conclusions: </strong>This study provides evidence for the association between the miR-34b/c rs4938723 polymorphism and hepatoblastoma risk in Chinese Han children from East China, suggesting that this polymorphism may have potential as a biomarker for predicting hepatoblastoma susceptibility in this specific population.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"105"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the molecular mechanisms, drug prediction, and validation of CCNA2 and MAD2L1 in esophageal squamous cell carcinoma based on bioinformatics.","authors":"Chenfan Guo, Pandeng Wang, Diemei Huang, Jianji Guo, Tao Liu","doi":"10.1186/s12920-025-02173-w","DOIUrl":"10.1186/s12920-025-02173-w","url":null,"abstract":"<p><strong>Objective: </strong>Aims to comprehensively investigate the expression patterns of CCNA2 and MAD2L1 in esophageal squamous cell carcinoma using bioinformatics methods.</p><p><strong>Methods: </strong>Based on WGCNA analysis of gene mutation expression, methylation level distribution, mRNA expression and ESCC-related genes in public databases, were employed for investigating potential biomarkers for prognosis of esophageal squamous cell carcinoma(ESCC).Finally,. performing qRT-PCR and immunohistochemistry to validate.</p><p><strong>Results: </strong>Ultimately identified 4 hub genes: CDK1, CCNA2,TOP2A and MAD2L1. Bioinformatics analysis showed high expression of these four genes in ESCC (P < 0.05). CCNA2 and MAD2L1 were selected for subsequent analysis based on literature.3.Single gene enrichment analysis revealed significant enrichment of CCNA2 and MAD2L1 in pathways related to splicing, bladder cancer, non-homologous end joining and homologous recombination, glycosaminoglycan biosynthesis chondroitin sulfate, progesterone-mediated oocyte maturation and mismatch repair. PASTAA database indicated the involvement of transcription factors such as Roralpha1, Pou6f1, Roralpha2, Atf-1, Pax-3, C/ebpalpha, Nkx2-1 in the regulation of CCNA2, while no transcription factors were predicted for MAD2L1..Immune infiltration analysis revealed a close association between ESCC and plasma cells, CD8 + T cells, monocytes, M0 macrophages, M1 macrophages, dendritic cells, and resting mast cells.Drug prediction for CCNA2 included 7 drugs such as ETHINYL ESTRADIOL, Seliciclib and TAMOXIFEN, while no drugs were predicted for MAD2L1.qRT-PCR and immunohistochemistry demonstrated high expression of CCNA2 in ESCC, while MAD2L1 showed no significant difference between ESCC and normal esophageal squamous epithelial tissues.</p><p><strong>Conclusion: </strong>CCNA2 and MAD2L1 may be potential biomarkers for ESCC, providing a novel basis for understanding the molecular mechanisms underlying ESCC pathogenesis.Additionally, the potential drugs predicted for CCNA2 may emerge as a new hope for ESCC patients in the future.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"107"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From gene expression to causal associations: investigating the role of ferroptosis in cataract development.","authors":"Chen Li, Xian-Bing Yuan, Yi-Cheng Lu, Zi-Yue Song","doi":"10.1186/s12920-025-02177-6","DOIUrl":"10.1186/s12920-025-02177-6","url":null,"abstract":"<p><strong>Background: </strong>Cataracts are one of the most prevalent blinding eye diseases globally, and ferroptosis may be involved in its pathogenesis; however, the precise mechanisms remain unclear. We therefore aimed to identify ferroptosis-related genes (FRGs) related to cataracts and assess their causal association.</p><p><strong>Methods: </strong>We downloaded two gene expression profile datasets of patients with cataracts and gathered the FRGs from the MSigDB and GeneCards databases. This allowed us to find the ferroptosis-related differentially expressed genes (FRDEGs). The potential functions of these FRDEGs were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), and gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was established, and hub genes were screened. Additionally, potential diagnostic markers were identified by RT-PCR validation. Finally, a Mendelian randomization (MR) study was performed to ascertain the causal impact of FRDEGs on cataracts.</p><p><strong>Results: </strong>Nineteen FRDEGs were identified by overlapping DEGs with FRGs. GO, KEGG and GSEA showed that the FRDEGs were associated with oxidative stress, IL17 signaling pathway, and glutathione metabolism. Nine hub genes were identified using the PPI network and five algorithms in Cytoscape. The RT-PCR results validated TIGAR, IL6, ATF3, and TNFAIP3 as potential biomarkers.</p><p><strong>Conclusion: </strong>TIGAR and IL6 were identified to be causally associated with cataracts. Inverse variance weighting revealed that TIGAR decreased the risk of cataracts, whereas IL6 increased the risk of cataract. Our research identified ferroptosis-related hub genes in cataracts, providing valuable insights for pre-symptomatic diagnosis and contributing to our understanding of the molecular mechanisms of cataract risk genes.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"111"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression analysis of LINC00671 and LINC01913 long non-coding RNAs in gastric cancer patients and their correlation with EMT markers.","authors":"Fatemeh Taghavinia, Negin Taghehchian, Iman Salahshourifar, Mohammad Reza Abbaszadegan","doi":"10.1186/s12920-025-02156-x","DOIUrl":"10.1186/s12920-025-02156-x","url":null,"abstract":"<p><strong>Background: </strong>Long-chain non-coding RNAs (lncRNAs) play various roles in the regulation of gene expression at the levels of transcription and translation, and epigenetic modification. Dysregulation of lncRNAs is associated with various malignancies, including cancer. lncRNAs have been demonstrated to regulate critical biological processes in cancer cells, such as apoptosis, proliferation, migration, and invasion. They also play essential roles in the development of gastric cancer (GC). However, the clinical significance and biological function of many lncRNAs remain unexplored in GC progression. This study aimed to evaluate the expression profiles of LINC00671 and LINC01913 in GC patients and investigate their correlation with epithelial-to-mesenchymal transition (EMT) markers.</p><p><strong>Method: </strong>The real-time PCR technique was applied to measure the expression levels of the selected lncRNAs (LINC01913 and LINC00671) and EMT-related mRNAs (MAMLs and MMP-13) in 83 tumor and adjacent normal tissues obtained from GC patients.</p><p><strong>Result: </strong>A significant reduction in LINC00671 expression was observed in 55.4% of tumor tissues, while elevated expression of LINC01913 (41%), MMP13 (56.6%), and MAML1 (44.6%) was detected, representing the proportion of samples with dysregulated expression relative to matched normal tissues. Dysregulation of these genes was significantly associated with various clinicopathological features (P < 0.05), supporting a potential link between these lncRNAs and EMT processes in GC.</p><p><strong>Conclusion: </strong>The observed associations between LINC00671, LINC01913, and EMT-related genes suggest their potential as prognostic biomarkers for treatment response in GC patients.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"109"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms.","authors":"Bowen Zheng, Jianxiong Qiao, Xiaoping Yu, Hanghang Zhou, Anqi Wang, Xuanfen Zhang","doi":"10.1186/s12920-025-02174-9","DOIUrl":"10.1186/s12920-025-02174-9","url":null,"abstract":"<p><strong>Background: </strong>Keloid disorder (KD) encompasses a spectrum of fibroproliferative dermal conditions, the pathogenesis remains complex and incompletely understood. This study sought to identify biomarkers and potential therapeutic targets for KD through an integrative bioinformatics approach and machine learning analysis of RNA sequencing data.</p><p><strong>Methods: </strong>RNA sequencing was performed on skin tissue samples from 13 patients with KD and 14 healthy controls. Using weighted gene co-expression network analysis and differential expression analysis revealed differentially expressed key module genes, and the CytoHubba plugin identified candidate genes. Subsequently analyzed using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) methods to pinpoint feature genes associated with KD. Following this, biomarkers were determined through expression level validation, enrichment analysis, and immune infiltration analysis.</p><p><strong>Results: </strong>A total of 420 differentially expressed key module genes were identified, and the top 10 genes with DMNC values were selected as candidate genes. Five feature genes were selected through LASSO and SVM-RFE, with NID2, MFAP2, COL8A1, and P4HA3 showing significant expression differences between KD and control samples, along with consistent expression patterns across datasets, identified as potential biomarkers. These four biomarkers were proved to possess high diagnostic potential, and they were found to exhibit significant positive correlations with one another. Functional enrichment analysis indicated that the primary KEGG pathways associated with these biomarkers included \"steroid hormone biosynthesis\" and \"cytokine-cytokine receptor interaction.\" Moreover, immune infiltration analysis revealed that the four biomarkers were negatively correlated with type 17 T helper cells and positively correlated with 15 immune cell types, including activated B cells and central memory CD4 T cells.</p><p><strong>Conclusion: </strong>In conclusion, NID2, MFAP2, COL8A1, and P4HA3 were identified as key biomarkers for KD, offering new avenues for more targeted and effective diagnostic and therapeutic strategies for managing this condition.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"108"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.","authors":"Xue Zhong, Xuan Zheng, Yinglei Xv, Kangxi Cai, Qianqian Wang, Shiguo Liu","doi":"10.1186/s12920-025-02157-w","DOIUrl":"10.1186/s12920-025-02157-w","url":null,"abstract":"<p><strong>Background: </strong>Adams-Oliver syndrome (AOS) is a rare developmental disorder, and the DOCK6 gene is an identified AOS gene. This report highlights the prenatal diagnosis of AOS-2 by ultrasonography and genetic testing.</p><p><strong>Methods: </strong>A growth-restricted fetus with bilateral ventriculomegaly, paraventricular calcifications, and ventricular septal defect underwent trio-whole-exome sequencing (trio-WES). Functional validation of the splice-altering variant was performed via minigene assays and protein structural modeling.</p><p><strong>Results: </strong>Trio-WES revealed compound heterozygous DOCK6 variants: a paternal frameshift (c.3190_3191del; p. Leu1064Valfs60) and a maternal splice-site variant (c.3241-1G > T). Minigene assays demonstrated that c.3241-1G > T caused intron 26 retention (486 bp), introducing a premature termination codon (p. Val1081Glufs37). Structural modeling confirmed the loss of critical DHR2 domains in both truncated proteins.</p><p><strong>Conclusions: </strong>This study expands the mutational spectrum of DOCK6 and underscores the importance of combining prenatal imaging with functional genomics for early diagnosis of AOS2.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"104"},"PeriodicalIF":2.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosomal instability by low-coverage whole-genome sequencing assay predicts prognosis in bladder cancer patients underwent radical cystectomy.","authors":"Qi Ding, Hailiang Zhu, Bo Fan, Lisheng Wang, Xiaohua Jin, Cheng Cao, Ying Shi, Zhijiang Fan, Wenjian Tu, Feng Li","doi":"10.1186/s12920-025-02172-x","DOIUrl":"10.1186/s12920-025-02172-x","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate chromosomal instability (CIN) in tumor tissue from radical bladder resection and to evaluate whether it can be used as a biomarker for the molecular typing of (BC).</p><p><strong>Methods: </strong>DNA was extracted from formalin-fixed paraffin-embedded samples of 50 BC patients who were followed up to March 23 2023 using the Qiagen nucleic acid kits. We analyzed CIN in tumor of bladder by low-coverage whole genome sequencing (LC-WGS). Kaplan-Meier log-rank test was used to perform survival analysis. The association between variables and overall and progression-free survival was analyzed using the Cox proportional hazards model.</p><p><strong>Results: </strong>There were 44 genome segments with statistically significant changes in copy number. CIN was significantly correlated with tumor stage, lymph node metastasis, relapse and survival status. Patients with high CIN were found to have a worse survival, with a median overall survival (OS) of 15 months. In addition, patients with high CIN were more likely to relapse, with a median progression-free survival (PFS) of 7 months. Patients with low CIN showed better OS and PFS. However, there was no significant difference in OS and PFS between T2 and T3-T4 patients. Multivariate cox regression analysis showed that high CIN was an independent predictor of OS, and high CIN and muscle invasion were independent predictors of PFS. Furthermore, patients with abnormal copy number of a single chromosome also had a poor prognosis, with a median survival of 14-30 months for OS and 5-10 months for PFS, while negative patients had a better prognosis.</p><p><strong>Conclusion: </strong>CIN was significantly correlated with tumor stage, lymph node metastasis, relapse and survival status of BC. Patients with high CIN or abnormal copy numbers of a single chromosome have a poor prognosis. CIN might be better than T stage in predicting the prognosis of patients with BC. Molecular typing of CIN can be used as an independent prognostic factor for BC.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"103"},"PeriodicalIF":2.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABO exon polymorphisms are related to ischemic stroke in a Chinese Han population.","authors":"Yi Zhong, Mei Lin, Xiaoli Zhou, Chanyi He, Qi Lin, Quanni Li, Yipeng Ding","doi":"10.1186/s12920-025-02170-z","DOIUrl":"10.1186/s12920-025-02170-z","url":null,"abstract":"<p><strong>Background: </strong>Recent research have underscored the relation of ABO blood group system to cerebrovascular disorders predisposition. The present investigation endeavors to delve into the relationship between ABO polymorphisms and ischemic stroke (IS) risk.</p><p><strong>Methods: </strong>A cohort of 646 IS patients and 649 matched healthy controls was recruited. Genotyping of five SNPs within ABO were conducted by Agena MassARRAY platform. Logistic regression models were employed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Additionally, SNP-SNP interaction was assessed by multifactor dimensionality reduction (MDR) method. Furthermore, Analysis of Variance (ANOVA) was utilized to explore the association between genotypes and blood lipid profiles.</p><p><strong>Results: </strong>The study identified an elevated IS risk associated with rs8176740 and rs8176720 in the overall population. Notably, ABO rs8176720 emerged as the most informative single-locus model for IS susceptibility. These variants were related to an elevated IS risk, specifically in female subjects, the subgroup aged > 64 years, non-smokers, drinkers or non-drinkers. Moreover, rs8176749 and rs8176745 were associated with red blood cell count levels and total bilirubin levels.</p><p><strong>Conclusion: </strong>This study firstly demonstrated the association of ABO rs8176740 and rs8176720 with IS incidence, which increased the understanding regarding the effect of ABO on IS pathogenesis.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"102"},"PeriodicalIF":2.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania.","authors":"Zhi Ming Xu, Michaela Zwyer, Hellen Hiza, Sarah Schmidiger, Mohamed Sasamalo, Miriam Reinhard, Anna Doetsch, Sonia Borrell, Olivier Naret, Sina Rüeger, Dylan Lawless, Simon Tang, Faima Isihaka, Hosiana Temba, Thomas Maroa, Rastard Naftari, Christian Beisel, Jerry Hella, Klaus Reither, Daniela Brites, Damien Portevin, Sebastien Gagneux, Jacques Fellay","doi":"10.1186/s12920-025-02164-x","DOIUrl":"10.1186/s12920-025-02164-x","url":null,"abstract":"<p><p>The risk and prognosis of tuberculosis (TB) are influenced by a complex interplay between human and bacterial genetic factors. While previous genomic studies have largely examined human and bacterial genomes separately, we adopted an integrated approach to uncover host-pathogen interactions. We leveraged paired human and Mycobacterium tuberculosis (M.tb) genomic data from 1000 adult TB patients from Tanzania and used a \"genome-to-genome\" approach to search for associations between human and M.tb genetic variants and to identify interacting genetic loci. Our analyses revealed two significant host-pathogen genetic associations. The first significant association (p = 4.7e-11) links a human intronic variant in PRDM15 (rs12151990), a gene involved in apoptosis regulation, with an M.tb variant in Rv2348c (I101M), which encodes a T cell-stimulating antigen. The second significant association (p = 6.3e-11) connects a human intergenic variant near TIMM21 and FBXO15 (rs75769176) - also associated with TB severity (p = 0.04) - with an M.tb variant in FixA (T67M). While FBXO15 is involved in the regulation of antigen processing and TIMM21 affects mitochondrial function, FixA's role remains undefined due to limited functional characterization. Additionally, we observed that a group of M.tb T cell epitope variants were significantly associated with HLA-DRB1 variation, suggesting that, despite their rarity, certain epitopes may still be subjected to immune selective pressure. Together, these findings identify previously unknown sites of genomic conflicts between humans and M.tb, advancing our understanding of how this pathogen evades selection pressure and persist in human populations.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"99"},"PeriodicalIF":2.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDA5 variants trade antiviral activity for protection from autoimmune disease.","authors":"Chris Wallace, Rahul Singh, Yorgo Modis","doi":"10.1186/s12920-025-02171-y","DOIUrl":"10.1186/s12920-025-02171-y","url":null,"abstract":"<p><p>Loss-of-function variants in MDA5, a key sensor of double-stranded RNA from viruses and retroelements, have been associated with protection from type 1 diabetes (T1D) in genome-wide association studies (GWAS). MDA5 loss-of-function variants have also been reported to increase the risk of inflammatory bowel disease (IBD). Whether these associations are linked or extend to other diseases remains unclear. Here, fine-mapping analysis of four large GWAS datasets shows that T1D-protective loss-of-function MDA5 variants also protect against psoriasis and hypothyroidism, while increasing the risk of IBD. The degree of autoimmune protection and IBD risk were linearly proportional. The magnitudes of the odds ratios for autoimmune protection and IBD risk were larger for rare MDA5 variants than for common variants, which were differentially expressed in different geographic populations. Our analysis suggests MDA5 genetic variants offer a direct fitness trade-off between viral clearance and autoimmune tissue damage.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"101"},"PeriodicalIF":2.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}