Genetics research最新文献

{"title":"Impact of Infection-Related Immune Responses on ANCA-Associated Vasculitis in Finns: A Mendelian Randomization Study.","authors":"Naidan Zhang, Caixia Ji, Tong Lv, Xiao Bao","doi":"10.1155/genr/3406375","DOIUrl":"10.1155/genr/3406375","url":null,"abstract":"<p><strong>Background: </strong>ANCA-associated vasculitis (AAV) includes microscopic polyarteritis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies have revealed that infection-related immune responses could trigger vasculitis. This study aims to investigate the relationship between infection-related immune responses and AAV in Finns.</p><p><strong>Methods: </strong>We used multiple Mendelian randomization (MR) methods and bioinformatics to examine how infection-related immune responses affect AAV, also investigating the mediation effects of neutrophil extracellular traps (NETs) and aging phenotypes. Bioinformatics data were from the Gene Expression Omnibus (GEO) database. Serum-specific antibodies were from the U.K. Biobank. AAV subtypes were from FinnGen. Single-cell sequencing data of immune cells were from the OneK1K database. NETs and aging phenotypes were from the genome-wide association studies (GWAS).</p><p><strong>Results: </strong>This study found a preliminary negative correlation between anti-IgG of HSV1 and the risk of MPA (OR: 0.499, 95% CI: 0.361-0.692, p = 3.05E-05). The SCeQTL analysis revealed that several genes in immune cells were linked to anti-IgG of HSV1 and MPA, while mediation analysis highlighted DNA methylation Hannum age acceleration (DNAmAA) as a key mediator between gene expression and MPA. HLA-C expression in CD8nc T cells (Z = -2.921, p = 0.003, mediation effect = 82.2%) and MDC1 in dendritic cells (Z = -3.310, p = 0.001, mediation effect = 81.5%) lowered the risk of MPA by downregulating DNAmAA. Conversely, MICA expression in NKR NK cells (Z = 3.702, p < 0.001, mediation effect = 72.1%) was associated with an increased risk of MPA by upregulating DNAmAA.</p><p><strong>Conclusions: </strong>This study demonstrated potential correlations between infection-related immune responses and MPA. The SCeQTL analysis revealed that HLA-C expression in CD8nc T cells, MDC1 in dendritic cells, and MICA expression in NKR cells were related to the risk of MPA. Furthermore, mediation analysis indicated that DNAmAA exerted a strong mediation effect on the relationship between gene expression and MPA.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e3406375"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Profiling of Germline Variants in the DNA Mismatch Repair Genes in Chinese Colorectal Cancer Patients.","authors":"Xiu Zhu, Da Han, Jun Chen, Jingjing Xu, Jiaoyue Jin, Qian Lai, Lina Xie, Jianfei Fang, Liu Zhu, Ying Yu, Jun Yang, Taoli Wang, Xueping Xiang, Xuejiang Shi, Desheng Xiao, Dan Su","doi":"10.1155/genr/9910339","DOIUrl":"10.1155/genr/9910339","url":null,"abstract":"<p><strong>Background: </strong>A multicenter study on the DNA mismatch repair (MMR) genes enabled us to study the profiling of germline variants in MMR genes of colorectal cancer (CRC) patients with MMR deficiency (dMMR). The clinicopathological differences between Lynch syndrome (LS) patients and sporadic dMMR CRC patients were compared by Student's t-test and χ² test. The molecular profiling of germline variants in MMR genes in Chinese CRC patients with dMMR is clarified.</p><p><strong>Methods: </strong>A total of 326 CRC patients with dMMR were enrolled. Next-generation sequencing (NGS) and Sanger sequencing were performed using tumor-adjacent tissues of enrolled patients. Four MMR genes (MLH1, MSH2, MSH6, and PMS2) are included in the NGS panel.</p><p><strong>Results: </strong>A total of 113 germline variants were detected, including 81 pathogenic and likely pathogenic variants. The clinicopathologic differences between CRC patients with/without LS were observed in age, family history, lesion location, and dMMR patterns. The CRC cohort with IHC-MSH6 negative alone shows the highest prevalence rate of LS. MLH1 was detected with the most germline variants. The mutational hotspot region of MLH1 is Exon 8, Exon 4 for MSH6, Exon 11 for PMS2, and Exon 7 for MSH2. Several germline hotspots were labeled on each MMR gene sequence by fixed-size bin analysis. In addition, some variants were novel discovered based on the presence or absence of the RS number and allele frequency record.</p><p><strong>Conclusions: </strong>Our study classified the clinicopathological features between sporadic CRC patients and LS patients. More importantly, the molecular profiling of the MMR gene germline variant was experimentally elucidated, which deepens the knowledge of MMR genes and provides a new perspective for the subsequent studies on the landscape of germline variants of Chinese LS patients.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e9910339"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency and Distribution of Incidental Chromosomal Abnormalities Detected by Peripheral Blood Karyotyping: A Retrospective Study.","authors":"Yaqin Zhang, Zongkai Bai, Rui Li, Han Yang, Jinfeng Wang, Yiying Chen","doi":"10.1155/genr/4906805","DOIUrl":"10.1155/genr/4906805","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to examine the frequency and distribution of incidental chromosomal abnormalities identified through peripheral blood karyotype analysis and to evaluate their associations with sex, age, and chromosomal characteristics.</p><p><strong>Methods: </strong>This retrospective study conducted an analysis of 2397 peripheral blood karyotype assessments carried out between September 2023 and February 2025. The study employed conventional lymphocyte culture and G-banding techniques, with karyotypes characterized in accordance with the International System for Human Cytogenomic Nomenclature (ISCN) 2024 guidelines. Chromosomal abnormalities that did not satisfy clinical reporting criteria were systematically documented. Detection rates were evaluated and compared across different sex and age groups, as well as chromosomal categories, utilizing chi-square tests and linear trend analysis.</p><p><strong>Results: </strong>A total of 511 cases of incidental chromosomal abnormalities were identified, yielding an overall detection rate of 21.32%. No statistically significant difference was observed in the detection rates of abnormalities between females and males (p > 0.05). However, significant differences were noted among various age groups, with detection rates exhibiting an increasing trend with advancing age (p < 0.05). The distribution of abnormalities was uneven across chromosomes, predominantly concentrated in the C and D chromosome groups. Chromosomes 7, 9, and 14 were the most frequently affected. The most prevalent types of abnormalities included balanced translocations, deletions, and inversions, with t(7; 14) and del(9) (q13) being the most commonly observed. Additionally, 23 marker chromosomes were identified, displaying considerable morphological variability.</p><p><strong>Conclusion: </strong>Incidental chromosomal abnormalities identified through peripheral blood karyotype analysis exhibit nonrandom distributions associated with variables such as age and specific chromosomes. These low-frequency occurrences may represent underlying somatic chromosomal variation and offer valuable reference data for the interpretation of karyotypes and the enhancement of laboratory quality control.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e4906805"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of Macrophage Dynamics, CCBE1, and Their Implications in Colorectal Cancer Microenvironment: Insights Into Tumor Progression and Therapeutic Opportunities.","authors":"XiaoFei Fan, ChunYan Zhang, RongRong Gu, Xin Xu","doi":"10.1155/genr/2678696","DOIUrl":"10.1155/genr/2678696","url":null,"abstract":"<p><strong>Background: </strong>The significance of M2 macrophages in cancer is well established, yet their specific role and the regulatory molecules involved in colorectal cancer remain unclear.</p><p><strong>Methods: </strong>Using publicly available single-cell RNA-seq data from four colorectal cancer datasets (EMTAB8107, GSE139555, GSE146771, and GSE166555), we evaluated macrophage proportions and their functional enrichment. Immune cell infiltration was quantified by CIBERSORT, quanTIseq, and xCell on TCGA-COAD bulk transcriptomes, with immune correlations adjusted for tumor purity. GSEA was performed with MSigDB v7.4 gene sets (Hallmark, GO, KEGG). Prognostic models were built using Kaplan-Meier and multivariate Cox regression. In vitro, CCBE1 was silenced in SW480 and HCT116 cells; proliferation was measured by CCK-8, colony formation, and EdU assays, and migration/invasion were measured by transwell assays. M2 polarization was assessed by flow cytometry.</p><p><strong>Results: </strong>Macrophages represented a substantial fraction (20%-35% across datasets) of the tumor microenvironment and were associated with upregulated coagulation and KRAS signaling. Consensus M2 macrophage infiltration was linked to 91 upregulated genes, among which CCBE1 emerged as an independent prognostic risk factor (multivariate Cox: HR = 1.305 [95% CI: 1.039-1.639], p < 0.05). CCBE1 was overexpressed in colorectal cancer cell lines compared to NCM460. Silencing CCBE1 significantly suppressed cell proliferation, migration, and invasion. Moreover, the conditioned medium from CCBE1-knockdown cancer cells decreased the proportion of CD206+ M2 macrophages and upregulated M1 markers while downregulating M2 markers, indicating that CCBE1 promotes M2 polarization.</p><p><strong>Conclusions: </strong>CCBE1 is an oncogenic driver in colorectal cancer that independently predicts poor survival and functionally enhances tumor cell proliferation, invasion, and M2 macrophage polarization. Targeting CCBE1 may represent a potential therapeutic strategy for colorectal cancer.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e2678696"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Subtype Classification and Mechanistic Investigation Based on Ferroptosis-Related lncRNAs in Ovarian Cancer.","authors":"Qianru Li, Mengyao Lv, Aijie Zhang, Xue Liu, Wanting Lu, Min Shao, Limian Cao","doi":"10.1155/genr/4503115","DOIUrl":"10.1155/genr/4503115","url":null,"abstract":"<p><p>Ovarian cancer (OC) ranks among the most prevalent malignant tumors in women, contributing significantly to mortality rates. This disease exhibits considerable heterogeneity, characterized by intricate molecular and genetic alterations. Ferroptosis, a distinct form of cell death, has emerged as a critical factor in various cancers, including OC. However, the regulatory mechanisms underlying ferroptosis in OC patients remain unclear and require further investigation. This study aimed to identify lncRNA associated with OC and elucidate the underlying mechanisms through bioinformatics methods and experimental validation. Ferroptosis-related lncRNAs (FRLs) was identified in OC, and its prognostic value was assessed using univariate Cox analysis. Additionally, the molecular subtypes of FRLs were evaluated through the ConsensusClusterPlus software package. Notably, Cluster 2 exhibited a low TME score, which was linked to a poorer prognosis. The GSEA suggested that Cluster 2 shared similarities with other clusters associated with worse survival outcomes, likely due to the activation of tumor-associated pathways. In vitro experiments further confirmed that certain lncRNAs could be upregulated under ferroptotic conditions. We focused on two lncRNAs, AC027348.1 and TRAM2-AS1, which were not noticed before and were significantly upregulated, to explore their regulatory effects on ferroptosis. The underlying mechanisms were preliminarily investigated through transcriptome sequencing. In summary, our findings offer new insights into the pathogenesis of OC, particularly regarding the role of lncRNAs related to ferroptosis.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e4503115"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the rs688 Polymorphism in the Gene Encoding Low-Density Lipoprotein Receptor in Bangladeshi Population With Coronary Artery Disease.","authors":"Imran Hossain, Nahid Sharmin, Istiaque Ahmed, Golam Saklayen, Sauda Sumaya Dina, Sheikh Zahir Raihan","doi":"10.1155/genr/5670428","DOIUrl":"10.1155/genr/5670428","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery disease (CAD) is among the leading causes behind the morbidity and mortality of the world population. Among others, low-density lipoprotein (LDL) is one of the main drivers behind the development of CAD, and the LDL receptor (LDLR) plays a central role in cholesterol homeostasis by facilitating the clearance of LDL cholesterol from the blood. The LDLR rs688 single-nucleotide polymorphism in exon 12 has been reported to influence mRNA splicing efficiency, potentially modifying receptor function and lipid metabolism. The aim of this study was to assess the association between LDLR rs688 polymorphism and CAD susceptibility among CAD patients in the Bangladeshi population and to determine its relationship with serum LDL level.</p><p><strong>Methods: </strong>A case-control study was conducted involving 225 participants, including 150 CAD patients and 75 healthy controls. High-density lipoprotein, LDL, triglycerides, and total cholesterol were measured by biochemical tests using appropriate kits. The LDLR genotype was identified using the allele-specific PCR (AS-PCR) technique.</p><p><strong>Results: </strong>Relative to the control group, the CAD group showed a higher distribution frequency of the TT genotype (17.33%) and a lower frequency of the CC genotype (15.33%). The LDLR rs688 TT genotype showed significant association with CAD among Bangladeshi patients (OR = 3.617, 95% CI: 1.089-10.05; p = 0.0352). Furthermore, individuals carrying the TT and CT genotypes exhibited higher LDL levels compared with those carrying the CC genotype (p < 0.05). Finally, univariate and multivariate logistic regression analyses revealed that the LDLR rs688 TT genotype remained significantly associated with CAD after adjustments for covariates (p < 0.05).</p><p><strong>Conclusion: </strong>This hospital-based case-control study provides preliminary evidence of an association between the LDLR rs688 TT genotype and CAD in a Bangladeshi population. These findings are preliminary and require validation in larger, population-based studies.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e5670428"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Causal Roles of Matrix Metalloproteinases in Metabolic Syndrome: A Mendelian Randomization Study Highlighting MMP12 in Blood Pressure Regulation.","authors":"Qiaohui Qian, Ming Fang, Zhaohua Gu, Yaming Yan, He Wen, Qian Sheng, Zeguo Shao, Xinming Li","doi":"10.1155/genr/1665162","DOIUrl":"10.1155/genr/1665162","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate whether matrix metalloproteinases (MMPs) are associated with the risk of metabolic syndrome (MetS) and its components.</p><p><strong>Methods: </strong>We conducted a two-sample Mendelian randomization (MR) study by using 9 types of MMPs as exposures and MetS and its components (waist circumference, essential hypertension, fasting blood glucose [FBG], high-density lipoprotein [HDL] cholesterol, and triglycerides) as outcomes. The genome-wide association study summary data of exposure and outcome were both obtained from publicly published research. Four MR analytical methods, including inverse variance weighted, MR-Egger, weighted median, and weighted mode, were applied to analyze the causality between exposure and outcome, in which IVW was employed as the primary analytical method. MR-Egger, Cochran's Q, leave-one-out (LOO), and MR pleiotropy residual sum and outlier (MR-PRESSO) were used to assess the reliability of the results of the MR analysis.</p><p><strong>Results: </strong>Genetically determined MMP12 showed significant negative associations to the risk of essential hypertension (OR = 0.996, 95% CI: 0.993-0.998, p = 0.001). Results that were analyzed with the MR-Egger, weighted median, and weight mode were consistent with those analyzed with IVW. Although MMP12 may have a suggestive protective effect on FBG levels (OR = 0.993, 95% CI: 0.986-1, p = 0.049), this finding may be affected by potential horizontal pleiotropy and requires further validation. No causal associations were identified between other MMPs and the risk of MetS or its components.</p><p><strong>Conclusions: </strong>This MR analysis provides evidence of causal links between MMP12 and the risk of essential hypertension, indicating that MMP12 might inform early risk stratification for specific cardiometabolic components (e.g., essential hypertension), rather than serving as a diagnostic biomarker for the composite metabolic syndrome.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e1665162"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Downregulation of hsa-miR-135b-5p Inhibits Cell Proliferation, Migration, and Invasion in Colon Adenocarcinoma.","authors":"Genetics Research","doi":"10.1155/genr/9859242","DOIUrl":"10.1155/genr/9859242","url":null,"abstract":"","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e9859242"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HRD-Driven Reprogramming of Macrophage Function and Spatial Architecture in High-Grade Serous Ovarian Cancer.","authors":"Hua Lan, Fang Xu, Linshuang Li, Xin Wei, Minghua Li","doi":"10.1155/genr/7364793","DOIUrl":"10.1155/genr/7364793","url":null,"abstract":"<p><p>High-grade serous ovarian cancer (HGSOC) exhibits homologous recombination deficiency (HRD), but its impact on the immune microenvironment remains unclear. Using single-cell RNA sequencing, spatial transcriptomic inference, and survival analyses, we characterized 166,895 macrophages across HRD subtypes: functional BRCA1/2 inactivation (FBI), HRD-Del (deletions), and HRD-Dup (duplications). FBI macrophages showed lipid metabolism enrichment (S100A8, CD36), HRD-Del macrophages upregulated antigen presentation (HLA-DQA1, HLA-DPB1), and HRD-Dup macrophages displayed interferon-stimulated gene expression (ISG15, MX1). Six macrophage subtypes (C1Q, FCN1, MARCO, MKI67, MMP9, S100A9) exhibited distinct spatial distributions and functions. MKI67+ macrophages correlated with improved survival, while C1Q + subsets predicted worse outcomes. HRD-Dup tumors with high macrophage signatures had better survival, suggesting a favorable immune landscape. Our findings reveal HRD-driven macrophage reprogramming as a key determinant of immune microenvironment composition and clinical outcomes, supporting HRD-specific macrophage-targeted therapies for HGSOC.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e7364793"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertension, Dyslipidemia, and Adhesive Capsulitis: A Bidirectional Two-Sample Mendelian Randomization Study of the European Population.","authors":"Jianxu Wang, Yijun Xin, Bin Li, Siying Li, Guang Yang","doi":"10.1155/genr/6618466","DOIUrl":"10.1155/genr/6618466","url":null,"abstract":"<p><strong>Background: </strong>Whether hypertension and dyslipidemia are risk factors for adhesive capsulitis (AC) remains controversial. Many observational studies have reported conflicting results. However, observational studies are susceptible to confounding and reverse causation, limiting the ability to establish causality. Therefore, a robust method is needed to clarify these relationships.</p><p><strong>Methods: </strong>We first conducted a hospital-based case-control study that included 200 AC patients and 200 controls. Multivariate logistic regression was used to examine the associations of hypertension and dyslipidemia with AC after adjusting for potential confounders. To address the inherent limitations of observational studies, we then performed a two-sample Mendelian randomization (MR) analysis. We obtained datasets related to essential hypertension, dyslipidemia, and AC from a public genome-wide association study (GWAS) database. Inverse variance weighted (IVW) served as the primary analysis method. Sensitivity analyses included MR-PRESSO to detect outliers and pleiotropy and Cochran's Q test (combined with MR-Egger and IVW) to assess heterogeneity. The robustness of the findings was evaluated using a leave-one-out analysis. Finally, a bidirectional MR analysis was conducted by swapping the exposures and outcomes to test for reverse causality.</p><p><strong>Results: </strong>In the clinical case-control study, multivariate logistic regression revealed that age (OR: per year: 1.061, 95% CI: 1.034-1.089, p < 0.001) and diabetes (OR: 2.153, 95% CI: 1.271-3.646, p = 0.004) were independently associated with AC, whereas neither hypertension (OR: 1.406, 95% CI: 0.870-2.274, p = 0.164) nor dyslipidemia (OR: 1.760, 95% CI: 0.912-3.395, p = 0.092) showed a significant association with AC. Consistent with the observational findings, MR analysis detected no causal effect of hypertension or dyslipidemia on AC. However, reverse MR analysis identified a significant negative causal effect of AC on high-density lipoprotein (HDL) cholesterol (OR: 0.989, 95% CI: 0.982-0.997, p = 0.008) and a positive causal effect of AC on the apolipoprotein B/A1 ratio (OR: 1.018, 95% CI: 1.001-1.034, p = 0.033).</p><p><strong>Conclusion: </strong>Our MR analysis revealed a negative causal effect from AC to HDL cholesterol and a positive causal effect from AC to the apolipoprotein B/A1 ratio. These findings provide evidence for the temporal sequence and reverse causal relationship between AC and dyslipidemia. The convergent results from both clinical and genetic analyses support the robustness of this causal relationship and highlight AC as a potential driver of lipid abnormalities. Therefore, these findings underscore the need for further experimental and mechanistic studies to elucidate the underlying biological mechanisms.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2026 1","pages":"e6618466"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}