Molecular Genetics and Genomics最新文献

{"title":"Whole exome sequencing uncovers novel genetic insights into Tethered cord syndrome.","authors":"Shuang Liu, Benzhang Tao, Gan Gao, Feng Zhang, Shuyan Tang, Lei Hou","doi":"10.1007/s00438-026-02490-4","DOIUrl":"10.1007/s00438-026-02490-4","url":null,"abstract":"<p><p>Tethered cord syndrome (TCS) is a neurodevelopmental disorder associated with neural tube defects (NTD), yet its genetic underpinnings remain poorly characterized. To elucidate its molecular basis, we conducted whole-exome sequencing (WES) on 81 TCS patients. Our analysis revealed that MNX1 variants, including two microdeletions and a deleterious missense variant, accounted for 3.7% (3/81) of cases in this cohort. Furthermore, gene-based collapsing analysis against 5,000 healthy controls revealed eight genes significantly enriched for loss of function variants and nine genes with an excess burden of damaging missense variants in TCS patients. Additionally, TCS patients exhibited a significantly higher burden of damaging missense variants in NTD-related genes. We also identified a trigenic variant combination (AFDN/PCSK5/PRICKLE4) exclusively in TCS patients, suggesting potential oligogenic inheritance in TCS. Collectively, our findings expand the genetic architecture of TCS, highlight novel pathogenic mechanisms, and provide insights for future clinical surveillance.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate derived from CAFs mediates H3K18la in stemness gene promoters, which promotes tumor malignant phenotype formation.","authors":"Jie Yao, Guangbin Li, Ke Chen, Yuxuan Wang, Xiaochen Lu, Jiaxi Li, Haitao Ma","doi":"10.1007/s00438-026-02460-w","DOIUrl":"10.1007/s00438-026-02460-w","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, characterized by high invasiveness, poor prognosis, and limited therapeutic options. Cancer-associated fibroblasts (CAFs), as a core component of the tumor microenvironment (TME), have been shown to promote the malignant progression of NSCLC, but the specific regulatory mechanisms remain incompletely understood. This study aims to investigate the role of CAFs and their metabolic products, particularly lactate, in the progression of NSCLC. CAFs and normal fibroblasts (NFs) were cultured, and the conditioned media (CM) were collected and used to treat NSCLC cells. Cell proliferation was assessed using CCK-8 and EdU assays, while cell migration was evaluated through transwell assays. The expression of E-cadherin and N-cadherin was detected by immunofluorescence (IF). Additionally, lactate levels, gene expression, and lactylation levels were assessed using a lactate detection kit, RT-qPCR, Western blot (WB), and chromatin immunoprecipitation (ChIP). The CM from CAFs enhanced the proliferation, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Our experiments revealed that the metabolites from CAFs, particularly lactate, had a promoting effect on NSCLC. In lactate-treated NSCLC cells, the expression levels of stemness genes were significantly upregulated, accompanied by increased lactylation levels of H3K18. In in vivo experiments, tumors from the lactate treatment group exhibited higher growth rates and increased expression of stemness genes. Furthermore, human NSCLC tumor tissues showed significant upregulation of stemness genes. This study demonstrates that lactate derived from CAFs promotes the expression of stemness genes by mediating H3K18 lactylation in the promoters of these genes in NSCLC cells, thereby accelerating the malignant phenotype formation of NSCLC cells. These findings provide new insights into the role of CAFs in the TME and identify potential therapeutic targets for NSCLC.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-SSR architecture in Acrossocheilus fasciatus links cross-assembly repeat conservation, repeat-unit count variation, and genomic context.","authors":"Kai Liu, Nan Xie","doi":"10.1007/s00438-026-02489-x","DOIUrl":"10.1007/s00438-026-02489-x","url":null,"abstract":"<p><p>Microsatellites, or simple sequence repeats (SSRs), are abundant genomic features, but their evolutionary interpretation is often limited by detector-dependent discovery and single-reference surveys that count repeats without resolving homologous repeat states. We characterized pan-SSR architecture in the cyprinid Acrossocheilus fasciatus by integrating four genome assemblies within the AF_xajfe coordinate system. Synthetic ground-truth calibration identified Tandem Repeats Finder as the most accurate and parameter-stable algorithm, and coordinate-anchored merging resolved 499,190 pan-SSR entries comprising 39,150 core, 235,720 dispensable, and 224,320 private components. In homologous shared components, repeat-unit count variation dominated polymorphism (26.2% of core and 22.4% of dispensable SSRs), whereas motif mutations and mixed polymorphisms each remained near 1%. Genomic context differed among categories: core SSRs were preferentially associated with genes and promoters, private SSRs showed the highest classified transposable element overlap, and DNA transposons showed the strongest local association. At 1-Mb genomic resolution, SSR density was inversely associated with GC content (Pearson r = -0.485; Spearman ρ = -0.547), indicating scale-dependent constraints on repeat accumulation. Independent resequencing of 130 libraries from eight river populations showed that neutral/core and gene-associated/core sets could be genotyped in low-depth short-read data and retained population-informative repeat-unit dosage variation, including separation of the QingYiJiang group in weighted principal-component summaries. Together, these results provide a detector-calibrated, coordinate-anchored strategy for repeat evolutionary analysis in non-model vertebrates by comparing homologous SSRs across heterogeneous public assemblies and show that repeat-unit count variation, gene- and transposable-element-associated context, GC background, and short-read genotypability jointly organize the pan-SSR landscape.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-population proteome-wide mendelian randomization study identifies likely causal proteins for cardiovascular diseases.","authors":"Hua Zhong, Jingjing Zhu, Shuai Liu, Hoi Tung Hilton Wong, Yiqiang Zhang, Hung N Luu, Qing Wu, Xuexia Wang, Lang Wu","doi":"10.1007/s00438-026-02458-4","DOIUrl":"10.1007/s00438-026-02458-4","url":null,"abstract":"<p><p>Blood proteins may play causal roles in cardiovascular diseases (CVDs) such as heart failure (HF) and peripheral artery disease (PAD). Proteome-wide Mendelian randomization (MR) has been widely used to prioritize drug targets for CVD in European populations, but its application to non-European populations remains limited. We conducted a proteome-wide MR analysis to evaluate the potential causal effects of 2,922 plasma proteins on five CVDs-atrial fibrillation (AF), coronary artery disease (CAD), HF, ischemic heart disease (IHD), and PAD. Analyses were performed across African (n = 931), East Asian (n = 262), and European (n = 10,840) populations using genetic instrument data from the UK Biobank cohort. Significant associations were further examined with genetic colocalization to strengthen causal inference. Using MR and colocalization analyses, we identified 53 significant protein-CVD associations across multi-populations, including 16 in African, six in East Asian, and 31 in European populations, respectively. Cross-population comparisons revealed four protein-CVD associations unique to African population and another four specific to East Asian population. Integration with clinical trial data prioritized 14 protein-disease pairs as promising candidates for therapeutic development or drug repurposing. Our findings highlight the value of proteome-wide MR in evaluating drug target applicability across populations. Several protein-disease associations were population-specific, emphasizing the need for inclusive genetic research to inform precision medicine in CVD prevention and treatment.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RMRP mediates neuroprotection as a downstream effector of RBM3 in human neuroblastoma SH-SY5Y cells.","authors":"Shuangping Ma, Xianting Liu, Yiming Xie, Yuxuan Han, Ning Wang, Shenxue Li, Binfeng Cheng, Fei Ju, Lei Wang","doi":"10.1007/s00438-026-02487-z","DOIUrl":"10.1007/s00438-026-02487-z","url":null,"abstract":"<p><p>As a non-coding RNA (lncRNA), the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is implicated in ribosome biogenesis. In recent years, its role in the neurodegenerative system has been reported; however, the molecular mechanism underlying RMRP-mediated neuroprotective effects remains elusive. In the present study, we identified that RMRP expression is regulated by the RNA-binding protein RBM3. The overexpression of RBM3 significantly upregulated RMRP transcription in SH-SY5Y neural cells, whereas RBM3 knockdown led to a marked reduction in RMRP expression. Furthermore, RNA Immunoprecipitation (RIP) assays confirmed the potential interaction between RMRP and RBM3. We then investigated the functional significance of RMRP regulated by RBM3 in Parkinson's disease (PD) cell models. Exogenous overexpression of RMRP strongly attenuated cytotoxicity induced by neurotoxins rotenone (ROT) and MPP⁺ in SH-SY5Y cells, as evidenced by decreased levels of cleaved poly ADP-ribose polymerase 1 (PARP1) and enhanced cell viability. Given that RBM3 exerts robust neuroprotective effects by accelerating global protein synthesis (GPS), we hypothesized that RMRP is a key mediator of RBM3-conferred neuroprotection. Consistent with this hypothesis, RMRP overexpression enhanced the activity of eukaryotic elongation factor 2 (eEF2), a hallmark of cellular GPS. Its stimulatory effect on GPS was further validated using a puromycin incorporation assay. Collectively, our data reveal that RMRP acts as a novel effector of RBM3 in stimulating cellular GPS and conferring neuroprotective effects in SH-SY5Y cells, providing a new therapeutic target for PD.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of the NPHP4 c.2999_3005del (p.Asn1000SerfsTer4) variant in an Iranian family with nephronophthisis-4.","authors":"Motahareh Jadidi, Shima Booali, Kolsoum InanlooRahatloo","doi":"10.1007/s00438-026-02494-0","DOIUrl":"10.1007/s00438-026-02494-0","url":null,"abstract":"<p><p>Nephronophthisis type 4 (NPHP4) is a rare genetic kidney disorder progressing to end-stage renal disease (ESRD). In this study, we aimed to identify the genetic cause of NPHP4 in a pedigree with three affected individuals. Whole-exome sequencing was performed on the proband, and variants were filtered, analyzed, and evaluated using in silico tools. Co-segregation analysis was conducted using Sanger sequencing. Protein modeling for the wild-type and mutant forms was performed using AlphFold3. We identified a homozygous deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of NPHP4, which co-segregated with the disease in the pedigree, demonstrating an autosomal recessive inheritance. 3D protein modeling predicted significant structural changes due to the truncation. The results of this study reveal a deletion variant NPHP4 c.2999_3005del (p.Asn1000SerfsTer4) that causes NPHP4 disease. This study, as a second report of a variant, reaffirms this very variant's pathogenicity and illuminates a critical locus prone to disruption, enhancing our understanding of genotype-phenotype correlations in NPHP4. The concurrence of independent observations of the same variants in NPHP4 emphasizing C-terminal truncation strengthens evidence that disruption of this region is clinically relevant in NPHP4-related disease. These findings together can provide improved understanding of the genetic basis of the disease, therefore better guidance for genetic counseling and family planning strategies for additional affected families.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-coverage paleo-genome research identifies a pathogenic mutation on EXT1 in a Qing-period Chinese individual with multiple osteochondromas.","authors":"Bangyan Wang, Haodong Chen, Fanhao Xi, Haoquan Bao, Hetong Wen, Panxin Du, Chenshuang Sun, Jianxue Xiong, Baoshuai Zhang, Xin Chang, Yawei Zhou, Chuan-Chao Wang, Shaoqing Wen","doi":"10.1007/s00438-026-02493-1","DOIUrl":"10.1007/s00438-026-02493-1","url":null,"abstract":"<p><p>Multiple osteochondromas (MO) is a rare bone disease with variable manifestations that make it difficult to distinguish from phenotypically similar diseases, both morphologically and radiologically. As a monogenic disorder associated with mutations in EXT1 or EXT2, ancient DNA analysis can provide genetically confirmed diagnoses and insights into the pathogenesis of suspected cases. To further investigate a previously reported suspected MO case from Qing-period Shandong, China, we generated ancient whole-exome sequencing data from the individual's petrous bone, yielding a mean sequencing coverage of 27.172×. We identified a pathogenic heterozygous mutation in the ligand-binding site Rossmann-2 subdomain of EXT1 (c.791T > C; p.Leu264Pro) with a sequencing depth of 17×, a mutation also found in an unrelated modern Latin American patient. Additionally, by predicting and analyzing the 3D structure of the EXT1 protein, we detected structural and functional damage. Our findings expand the known spectrum of EXT1 mutations and enhance the comprehensive genotype-phenotype map of rare MO, providing insights into its genetic pathology from a historical perspective. Furthermore, this research expands the understanding of disease landscapes in Northern China, both paleopathologically and paleogenetically.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of artificial intelligence in advancing molecular biology in Africa: a narrative review.","authors":"Daniel Awuah, Alphonse Hounkpe, Jesse Anane-Asamoah, William Kanmwaa Dakubo, Isaac Kofi Adu, Prince Amoah Barnie, Emmanuel Owusu Ansah, Kwadwo Fosu, Cara Obenewaa Aidoo, Victoria Essien, Yakubu Adam, Ernest Ninson, Richard Quansah, Foster Kyei","doi":"10.1007/s00438-026-02492-2","DOIUrl":"10.1007/s00438-026-02492-2","url":null,"abstract":"<p><p>Artificial intelligence (AI) is rapidly becoming a core methodological pillar of molecular biology and precision medicine, and Africa is a uniquely consequential setting for this transition because the continent combines the world's greatest human genomic diversity with the most severe underrepresentation of that diversity in the datasets and reference resources on which AI models are built and benchmarked. This narrative review examines, for a genetics and genomics readership, where AI-driven methods are already strengthening African molecular biology, where the supporting evidence remains preliminary, and what is required to translate technical capability into scientifically robust and equitable benefit. The central argument is that AI is especially consequential in African molecular biology, not simply because it automates analysis, but because it can help unlock insight from African genomic diversity, pathogen biology, and clinically relevant multi-omics data that remain underrepresented in global models. Across core molecular domains, AI is accelerating protein structure prediction, high-throughput variant calling and pan-genomic reference construction, genome-wide association analysis, transcriptomic interpretation, drug discovery, and CRISPR guide design. African initiatives such as H3Africa, the African Genome Variation Project, H3ABioNet, and the H3D Centre show that locally generated datasets and African-led computational pipelines can already support meaningful discovery, from improved variant interpretation to structure-guided therapeutic prioritization. At the same time, persistent barriers remain, including underrepresentation of African genomes in training data and reference genomes, uneven computational infrastructure, limited interdisciplinary training, fragmented governance, and the risk that AI-derived benefits will remain inaccessible to the populations whose data enable them. We conclude that the future impact of AI in African molecular biology will depend less on adopting global tools in the abstract and more on building African-led datasets, validation pipelines, governance frameworks, and translational pathways that make molecular discovery both scientifically robust and equitably useful. Looking ahead, the central perspective offered by this review is that Africa's exceptional genomic diversity should be treated as a scientific asset rather than an analytical liability: realising this will require population-representative pan-genome references, sustained computational capacity, and governance structures that ensure African populations are not only the source of the underlying data but also the principal beneficiaries of the discoveries it enables.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNA LOXL1 antisense RNA 1 promotes the malignancy of non-small cell lung cancer cells via modulating the microRNA-122-5p/E2F transcription factor 3 axis.","authors":"Zhijian Wang, Zhenkui Zhang, Liqiang Zhao, Aiwen Sun, Min Wang","doi":"10.1007/s00438-026-02485-1","DOIUrl":"10.1007/s00438-026-02485-1","url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA) antisense RNA 1 (LOXL1-AS1), reportedly, exerts carcinogenic effects in cancers including non-small cell lung cancer (NSCLC) via competitive endogenous RNA (ceRNA) mechanism. Additionally, previous studies have implied that microRNA-122-5p (miR-122-5p) and E2F transcription factor 3 (E2F3) have cancer-promoting properties and tumor-suppressive properties, respectively. Here we aim to further explore the function and mechanism of LOXL1-AS1 in NSCLC. In this experimental study, we found that LOXL1-AS1 was high expression in NSCLC tissues and cell lines. High LOXL1-AS1 expression was significantly relevant to the advanced tumor node metastasis (TNM) stage and positive lymph node metastasis of NSCLC patients. LOXL1-AS1 overexpression promoted proliferation, migration and invasion of NSCLC cells, while LOXL1-AS1 knockdown had the opposite effect. LOXL1-AS1 could sponge miR-122-5p. E2F3 was a downstream target of miR-122-5p. LOXL1-AS1 increased E2F3 expression through repressing miR-122-5p. In addition, miR-122-5p up-regulation or E2F3 knockdown could offset the promoting effect of LOXL1-AS1 overexpression on proliferation, migration and invasion of NSCLC cells. Overall, this study demonstrates that LOXL1-AS1 promotes NSCLC cell proliferation and migration in vitro, and correlates with poor clinical outcomes, partially via modulating miR-122-5p/E2F3 axis.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A genetic signal at 8q12.3 modulates GGT levels via the Runx1-CYP7B1 axis in female ethnic minorities from Guizhou.","authors":"Qinghai Yao, Ji Chen, Tingting Yang, Changgui Lei, Shuang Zeng, Fei Luo, Feng Hong, Xin Jin","doi":"10.1007/s00438-026-02484-2","DOIUrl":"10.1007/s00438-026-02484-2","url":null,"abstract":"<p><p>Gamma-glutamyl transferase (GGT) regarded as a biomarker of liver dysfunction or excessive alcohol consumption; however, existing genome-wide association studies (GWAS) have been conducted predominantly in European populations and East Asian populations from Japan and the Taiwan region, with limited investigation in ethnic minorities from Guizhou Province. Previous genetic studies have demonstrated that Guizhou ethnic minorities share an East Asian genetic background while exhibiting specific genetic structures, a pattern that is also confirmed by our principal component analysis (PCA) results. We therefore performed a GWAS in this population and identified a genome-wide significant signal at 8q12.3 in female ethnic minorities from Guizhou. Fine-mapping and functional annotation analyses suggest that a regulatory pathway involving Runt-related transcription factor 1 (Runx1)-Cytochrome P450 family 7 subfamily B member 1 (CYP7B1)-cholesterol-reactive oxygen species (ROS)-glutathione (GSH) may contribute to the regulation of GGT levels. Mendelian randomization (MR) analyses further supported a causal relationship between GGT levels and autoimmune hepatitis (AIH). These findings uncover a genetic mechanism underlying GGT variation at 8q12.3 in female ethnic minorities from Guizhou, implicating a pathway linked to cholesterol metabolism and oxidative stress, and providing potential targets and insights for precision prevention and treatment of related diseases.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}