Human Genomics最新文献

{"title":"Genetic diagnosis in fetal hydronephrosis: assessment using chromosomal microarray analysis and whole-genome sequencing.","authors":"Jing Wang, Jingyu Zhao, Wei Wang, Xinmei Zhu, Bin Zhang, Bin Yu","doi":"10.1186/s40246-026-00950-x","DOIUrl":"10.1186/s40246-026-00950-x","url":null,"abstract":"<p><p>BACKGROUND: Antenatal hydronephrosis (AHN) is a common urological abnormality identified during prenatal ultrasound examination, with heterogeneous underlying causes. This study aimed to investigate the genetic etiologies of AHN using chromosomal microarray analysis (CMA) and whole-genome sequencing (WGS), and to identify the relationship between changes in AHN severity and genetic abnormalities. METHODS: Fetuses with AHN underwent CMA, followed by retrospective WGS. Detection rates of chromosomal abnormalities and monogenic variants were compared among different AHN types and between fetuses with downgraded versus persistent or upgraded hydronephrosis. A variant of uncertain significance (VUS) affecting a splice site was functionally validated using a minigene-splicing assay, leading to reclassification. RESULTS: Chromosomal abnormalities were detected in five of 54 fetuses (9.26%) using CMA, while WGS identified monogenic variants and chromosomal abnormalities in 10 of 54 (18.52%). The detection rate was significantly higher in AHN with extrarenal system malformations than in isolated AHN or AHN with renal tract malformations (p < 0.05). Fetuses with downgraded AHN had a lower detection rate (6.25%) than those with persistent or upgraded hydronephrosis (23.68%, p = 0.249). A novel GREB1L splice-site variant (c.2557G > A) caused aberrant splicing and was reclassified as likely pathogenic. CONCLUSIONS: WGS demonstrates higher diagnostic efficiency over CMA for AHN. Persistent or worsening AHN warrants timely genetic testing, and functional assays are critical for resolving VUS in prenatal diagnosis.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-trait genomic and sequential analyses of multiple omics datasets identified shared genetic components for the gut-eye axis.","authors":"Yuelan Gao, Jianming Xu, Jun Yu, Yuyao Wang, Yuzhou Zhang, Ka Wai Kam, Mary Ho, Alvin L Young, Chi Pui Pang, Clement C Tham, Jason C Yam, Li Jia Chen","doi":"10.1186/s40246-026-00947-6","DOIUrl":"10.1186/s40246-026-00947-6","url":null,"abstract":"<p><p>BACKGROUND: The gut–eye axis (GEA) has been proposed as a framework for understanding comorbidity between gastrointestinal and ocular diseases. This study aimed to investigate their shared genetic architecture, pleiotropy, and putative biological pathways potentially influenced by environmental exposures and gut microbiota. METHODS: This study integrated large-scale genome-wide association study summary data on five gastrointestinal and eight ocular diseases to assess genetic correlations and genetic overlap. Pleiotropic variants were identified, followed by functional and tissue-specific analyses. Gene–environment (G×E) interactions were evaluated using UK Biobank data. Mendelian randomization (MR) and mediation analyses were adopted to assess statistically inferred associations and potential mediating relationships involving gut microbiota. RESULTS: Extensive genetic correlations were identified between 40 trait pairs. In total, 366 pleiotropic loci were identified, with 21 loci showing evidence of colocalized shared signals. Notably, 2p21, 4q24, 19q13.32 and 5p15.31 were colocalized across 2 trait pairs, highlighting them as recurrent pleiotropic loci of potential interest. Of the 603 genes associated with pleiotropic variants, 261 recurred across two or more trait pairs. These genes were enriched in immune and inflammatory pathways and included well-known loci such as HLA-B and RBFOX1. Twenty-six pleiotropic variants interacted with 16 modifiable exposures (e.g., diet, mental health, BMI, smoking, physical activity), suggesting that G×E interactions may contribute to gut–eye comorbidity risk. Bidirectional MR identified 11 genetically predicted associations, while mediation analysis suggested a potential statistical association involving the polyamine biosynthesis pathway in the relationship between gastroesophageal reflux disease and diabetic retinopathy. CONCLUSIONS: This study characterizes shared genetic and environmental architecture across GEA-related disorders and highlights putative contributions from immune-related pathways and gut microbiota to disease comorbidity. Our findings provide a hypothesis-generating framework for future replication and experimental validation. </p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic spectrum of 11p15.5 duplications: parent-of-origin and copy number variant size shape outcomes from Silver-Russell to Beckwith-Wiedemann syndromes.","authors":"Chenyang Wang, Hengyuan Zhang, Meiying Wang, Juan Gao, Yibing Lv, Jianmei Huang, Shuxian Pan, Dong Wu, Bing Kang, Qiaofang Hou, Shixiu Liao","doi":"10.1186/s40246-026-00942-x","DOIUrl":"10.1186/s40246-026-00942-x","url":null,"abstract":"<p><p>BACKGROUND: Genomic imprinting at the 11p15.5 region is critically involved in fetal growth regulation. Disturbances in this region are primarily associated with two opposing growth disorders: Silver-Russell syndrome (SRS, growth restriction) and Beckwith-Wiedemann syndrome (BWS, overgrowth). While epigenetic alterations are well-characterized in SRS and BWS, copy number variants (CNVs) rearrangements remain incompletely understood, particularly in terms of how duplication size and parental origin shape the phenotypic spectrum. METHODS: We present a case series of three prenatally identified fetuses with 11p15.5 duplications, characterized by chromosomal microarray analysis and Methylation-Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA). Parental origin was determined by segregation analysis. RESULTS: Case A: A focal duplication of the maternally inherited allele encompassing only the ICR2/CDKN1C domain presented with severe isolated intrauterine growth restriction (IUGR), consistent with a SRS phenotype. Case B: A large duplication of the maternally inherited allele spanning both the ICR1/H19/IGF2 and ICR2/CDKN1C domains resulted in a complex phenotype of IUGR (SRS-like) with omphalocele (a BWS-associated anomaly), demonstrating a mixed and paradoxical presentation. Case C: A large duplication of the paternally inherited allele of the entire 11p15.5 region was associated with a BWS phenotype, presenting with macrosomia and other features, consistent with the predominant effect of paternal inheritance. CONCLUSION: Our findings support a model in which parental origin shows a strong tendency to determine the direction of growth dysregulation (maternal allele duplications predominantly associate with SRS-like restriction; paternal allele duplications with BWS-like overgrowth), while duplication size contributes to phenotypic complexity, with larger rearrangements involving both ICRs more frequently associated with severe or blended features. However, exceptions to this generalization exist in the literature, highlighting that 11p15.5 duplication disorders exhibit variable penetrance and expressivity. </p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cross-scale multimodal framework identifies clinically actionable immunotherapy biomarkers in melanoma through bulk to single-cell and spatial transcriptomics integration.","authors":"Wuda Huoshen, Kun Yuan, Junkai Xiong, Yilong Lin, Wenjie Yu, Yun Xie, Qian Yuan, Xinyue Zhang, Changqing Dong, Chen Sun, Sha Yi","doi":"10.1186/s40246-026-00919-w","DOIUrl":"10.1186/s40246-026-00919-w","url":null,"abstract":"<p><p>BACKGROUND: Melanoma, a type of skin cancer that can spread to other parts of the body, currently lacks highly precise individualized treatment options. METHODS: We performed multi-omics integration on The Cancer Genome Atlas Skin Cutaneous Melanoma (TCGA-SKCM) cohort to identify melanoma molecular subtypes. The identified genes were validated in independent meta cohorts from GEO, followed by transcriptome-wide association study (TWAS) validation using Genotype-Tissue Expression (GTEx) and UK Biobank datasets. Additionally, we analyzed machine learning-driven signature (CMLS) development, tumor microenvironment characteristics, immunotherapy response, and potential therapeutic targets. Finally, single-cell and spatial transcriptomics provided further biological insights and the pathomechanisms. RESULT: Our study identified two distinct molecular subtypes of SKCM using multimodal data integration with the MOVICS package: Cancer Subtype 1 (CS1) and CS2. CS2 showed a better prognosis and was enriched in immune-suppressive pathways such as WNT–β signaling, while CS1 exhibited higher activation of the PI3K pathway and DNA repair mechanisms, along with greater tumor invasiveness. TWAS analysis results combined the findings from TCGA-SKCM and the meta-cohort, identifying six significant prognostic-related genes (SPRGs). The CMLS prognostic model, based on SPRGs (CAP2, SELL, and LAPTM5 as risk factors and GZMA, FCER1G, and LYZ as protective factors), stratified patients into high-group (poorer survival) and low-risk groups. Single-cell and spatial transcriptomic analyses further validated CMLS prognostic results, highlighting distinct tumor microenvironment interactions and progression trajectories. CONCLUSION: Identifications of molecular subtypes and CMLS represent a valuable tool for early prediction of patient prognosis and for screening potential candidates likely to benefit from immunotherapy, with broad implications for clinical practice foundation for personalized therapies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the potential carcinogenic risk of bisphenols: a comprehensive network analysis and computational toxicology insights.","authors":"Tiegang Li, Zheng Yan, Wenyi Zhao, Yufang Hou, Silin Lv, Zifan Zeng, Liu Yang, Mingxuan Zhou, Fang Zhang, Xinyi Ren, Yixin Zhou, Zengni Zhu, Siying Huang, Min Yang","doi":"10.1186/s40246-026-00948-5","DOIUrl":"10.1186/s40246-026-00948-5","url":null,"abstract":"<p><p>PURPOSE: Bisphenols (BPs), including bisphenol A (BPA) and its analogs BPB, BPF, BPS, and BPAF, are essential industrial raw materials used in the production of consumer goods but pose significant public health risks. Bisphenols contribute to carcinogenesis due to their endocrine-disrupting properties, particularly in breast cancer. However, the relationship between BPs exposure and putative cancer risk, as well as the underlying molecular mechanisms, remains poorly understood. METHODS: This study employed network toxicology, molecular docking, molecular dynamics simulation, machine learning, and bioinformatics to systematically investigate the molecular mechanisms and potential targets associated with carcinogenic risks of five BPs. RESULTS: The findings revealed that BPs exposure increases cancer risk by targeting 26 core proteins, including RXRA, AKT2, and CYCS, leading to oxidative stress and modulation of cancer-related signaling pathways such as MAPK, PI3K/AKT, Ras, and VEGF. Molecular docking and dynamics simulations demonstrated stable binding interactions between RXRA and all five BPs. Analysis of the TCM database indicated that Ginseng, Turmeric, and Salvia miltiorrhiza can mitigate BPs-induced cancer risk by targeting these core proteins. Pan-cancer analysis showed that kidney renal clear cell carcinoma (KIRC) and low-grade glioma (LGG) are most strongly associated with BPs exposure. Diagnostic and prognostic models based on core targets exhibited high predictive accuracy, offering valuable clinical decision support. Single-cell sequencing revealed that core targets are primarily localized in immune cells in KIRC and glioma cells in LGG. CONCLUSION: This study provides a theoretical foundation for evaluating cancer risk associated with BPs exposure and establishes a novel framework for understanding the pathogenesis and potential therapeutic strategies for environmental pollutants.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolving non‑coding splice‑altering variants using an integrative genomic and transcriptomic workflow: application to FOXP1.","authors":"Pauline Planté-Bordeneuve, Anne-Sophie Jourdain, Caroline Thuillier, Aurélien Caux, Marine Tessarech, Jean-Pascal Meneboo, Emilie Ait-Yahya, Sara Costantini, Perrine Brunelle, Thomas Smol","doi":"10.1186/s40246-026-00946-7","DOIUrl":"10.1186/s40246-026-00946-7","url":null,"abstract":"<p><p>Genome sequencing (GS) often reveals non-coding variants of uncertain significance, especially those predicted to affect pre-mRNA splicing. We present an integrative workflow combining splice prediction, a minigene assay and long-read RNA sequencing to assess their functional impact. Applied to a de novo heterozygous 17-bp intronic deletion in FOXP1 from a child with a neurodevelopmental disorder, this approach showed impaired exon recognition and multiple aberrant transcript isoforms, supporting a loss-of-function mechanism consistent with FOXP1 haploinsufficiency. Our results illustrate how experimental and isoform-resolved transcriptomic analyses can refine the interpretation of non-coding splice-altering variants detected by GS in clinical genomics.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive analysis of the interaction network of immunomodulatory-related differentially expressed genes, aiming to identify biomarkers associated with Parkinson's disease.","authors":"Jianying Gao","doi":"10.1186/s40246-026-00929-8","DOIUrl":"10.1186/s40246-026-00929-8","url":null,"abstract":"<p><p>BACKGROUND: Parkinson's disease (PD) is a multifactorial neurodegenerative disease that results from the interplay of genetic, environmental, and immunological factors. In order to find biomarkers linked to PD, the current study intends to thoroughly explore the interaction network of immunomodulatory-related differentially expressed genes (IMRDEGs). METHODS: GeneCards database was used to obtain immunomodulation-related genes (IMRGs), and GEO database was used to obtain the expression profile dataset of GSE224913 and GSE99039 in patients with Parkinson’s disease. Using the limma package, we performed differential analysis to identify differentially expressed genes. Subsequently, we used GO, KEGG and GSEA for enrichment analysis of these differentially expressed genes. In addition, we constructed interaction networks between MRnas and transcription factors (TF), mrnas and drugs, and investigated protein–protein interaction networks (PPIs). Finally, CIBERSORT method was used for immunoinfiltration analysis to estimate the composition and abundance of immune cells. RESULTS: A total of 6 IMRDEGs were identified in the GSE224913 and GSE99039 datasets. The main focus of enrichment analysis is on immune-related pathways, including dendritic cell development and negative regulation of leucocyte mediated immunity. Most immune cells were associated with 6 IMRDEGs; The associations were highest with neutrophils, static NK cells, and T cells with active CD4 memory. In addition, regulatory networks of mRNA-TF, mRNA-miRNA and mRNA-Drugs target genes were established. CONCLUSION: In summary, the six core genes (HLA-B, HNRNPA, LILRB1, PARK7, S100A9, and SPI1) play pivotal roles in the progression of PD. The interaction networks encompassing mRNA-TF and mRNA-drugs contribute significantly to our understanding of disease progression and the optimization of treatment strategies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging proteomics and machine learning for mechanism and biomarker discovery on glioma progression and transformation: from LGG to GBM.","authors":"Qinhong Huang, Hui Liang, Jie Liu, Shenbao Shi, Xinlin Sun, Yiquan Ke, Taoliang Chen","doi":"10.1186/s40246-026-00945-8","DOIUrl":"10.1186/s40246-026-00945-8","url":null,"abstract":"<p><strong>Background: </strong>Glioma was the most common malignant tumor of the central nervous system in adults. Low-grade gliomas (LGGs) have a potential of grade progression and histological transformation, and the relevant mechanisms of this malignant evolution were still unclear.</p><p><strong>Methods: </strong>In this study, we used 61 primary-recurrent paired glioma samples from 28 patients for proteomics analysis based upon DIA-NN approach.</p><p><strong>Results: </strong>Our results indicated that the Ras/p38-MAPK pathways were hub signaling pathways driving grade progression and histological transformation in LGG. The activation of non-MGMT dependent unspecific DNA damage repair system mediated by Replication Factor C (RFC) can be an important reason for the treatment resistance. Moreover, metabolic reprogramming was widely involved in the regulation of LGG grade progression and histological transformation. The enhanced synthesis of unsaturated fatty acids and the significantly activated peroxisomal fatty acid beta-oxidation pathways were metabolic characteristics of LGG after histological transformation. Last, we constructed a reliable LGG progression prediction model consisted of 2 proteins, which can be monitor biomarkers for LGG progression, with potential clinical translation value.</p><p><strong>Conclusions: </strong>In summary, glioma grade progression and histological transformation were complex biological processes, which involved the abnormal up-regulation of Ras/p38-MAPK signalings, enhanced non-MGMT dependent unspecific DNA damage repair system regulated by RFC complex and metabolic reprogramming based on HK1-PFKP-ENO2 mediated glycolysis and peroxisomal FA beta oxidation. This study filled the gap in relevant research on the grade progression and histological transformation of LGG, providing novel and unique insights into the biological mechanisms of glioma progression.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic corepressor BCORL1 predominates as a driver of clonal hematopoiesis of indeterminate potential in patients undergoing chronic hemodialysis: a multicenter cohort study.","authors":"Kuan-Chieh Wang, Wei Wang, Chiung-Ying Huang, Szu-Ying Lee, Shih-I Chen, Cheng-Fong Tsai, Chien-Yuan Chen, Yi-Ting Chen, Yu-Hsiang Chou","doi":"10.1186/s40246-026-00944-9","DOIUrl":"10.1186/s40246-026-00944-9","url":null,"abstract":"<p><strong>Background: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant condition characterized by somatic mutations in hematopoietic stem cells in the absence of hematologic malignancy. CHIP predominantly affects older adults and is associated with increased risks of hematologic malignancy, cardiovascular events, and all-cause mortality. However, data on the prevalence, mutational spectrum, and clinical implications of CHIP in Asian patients with end-stage kidney disease (ESKD) undergoing chronic hemodialysis remain limited. Moreover, whether specific CHIP-associated genes confer distinct clinical characteristics or prognostic implications in this population remains unclear. In this prospective study, peripheral blood samples were obtained for whole-exome sequencing to identify CHIP-associated mutations. Clonal cytopenia of undetermined significance (CCUS) was defined as the presence of CHIP in patients with persistent cytopenia without an identifiable cause. The primary outcome was all-cause mortality, while secondary outcomes included major adverse cardiovascular events and malignancy.</p><p><strong>Results: </strong>61 patients with ESKD undergoing chronic hemodialysis were included and followed for a mean of 2.1 years. CHIP-associated mutations were detected in 50 patients (81.9%), who were classified as CHIP only (n = 8) or CCUS (n = 42), while 11 patients had no CHIP or CCUS. According to the Clonal Hematopoiesis Risk Score, patients with CHIP or CCUS were further stratified into low-, intermediate-, and high-risk groups. BCORL1 was the most frequently mutated gene (24.7%), followed by GNAS, BCOR, DNMT3A, ASXL1, and ATM, and remained predominant across all risk categories. BCORL1 mutations were more prevalent than DNMT3A mutations, particularly in CCUS. Unlike DNMT3A, which showed a clear age-dependent increase, BCORL1 mutations peaked between 50 and 70 years of age. At baseline, patients with BCORL1 mutations had a higher prevalence of cardiovascular disease and lower serum albumin levels. However, overall mortality and other clinical outcomes did not differ significantly during follow-up.</p><p><strong>Conclusions: </strong>CHIP in Asian patients undergoing chronic hemodialysis shows a high prevalence and a distinct mutation spectrum dominated by BCORL1. These findings suggest disease- and ancestry-specific selective pressures beyond aging and support gene-specific risk stratification and closer hematologic surveillance. Further multi-ethnic studies are needed to define the cardiovascular and hematologic implications of BCORL1-associated CHIP.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carrier rates for recessive monogenic diseases in the Chinese Han population: a systematic review.","authors":"Yirong Xia, Yinan Ma","doi":"10.1186/s40246-026-00940-z","DOIUrl":"10.1186/s40246-026-00940-z","url":null,"abstract":"<p><p>OBJECTIVE: In China, research on expanded carrier screening (ECS) has exhibited significant inconsistencies due to regional variations, with a lack of large-scale data analysis of the population nationwide. This study aimed to review the carrier rates of monogenic disorders throughout China comprehensively. METHODS: The study was conducted in two stages, with the carrier rate of monogenic diseases as the primary outcome. In the first stage, 1449 articles were identified, of which 11 were ultimately included for data extraction. In the second stage, all 307 genes identified by the first stage were specifically investigated, and both carrier rates and allele frequencies of pathogenic or likely pathogenic (P/LP) variants were extracted. RESULTS: Nineteen genes were associated with monogenic disorders exhibiting carrier frequencies above 1/100, including GJB2 (7.78%), HBA1/2 (6.19%), PAH (2.76%), ATP7B (2.51%), DUOX2 (2.50%), HBB (2.48%), GALC (2.37%), CYP21A2 (2.11%), SLC26A4 (1.96%), POLG (1.92%), USH2A (1.91%), SLC25A13 (1.87%), SLC22A5 (1.78%), SMN1 (1.75%), MMACHC (1.66%), G6PD (1.38%), GAA (1.05%), UGT1A1 (1.02%), and TYR (1.01%). Twenty-seven conditions had carrier rates between 1/100 and 1/200, and thirty had carrier frequencies between 1/200 and 1/400. The ten most common pathogenic/likely pathogenic (P/LP) variants with the highest allele frequencies were: GJB2 c.109G>A (7.3%), POLG c.2890C>T (0.94%), GALC c.1901T>C (0.90%), SMN1 exon 7 deletion (0.87%), SLC25A13 c.2T>C (0.59%), SLC22A5 c.1472C>G (0.52%), GJB2 c.235del (0.50%), SLC22A5 c.1400C>G (0.48%), SLC22A5 c.43G>T (0.44%), and SLC25A13 c.852_855del (0.43%). CONCLUSION: This review provides the first comprehensive summary of carrier rates for monogenic diseases in the Chinese Han population. It not only describes but also ranks the carrier rates and variant frequencies of related genes, offering critical evidence for the tiered inclusion of gene categories in ECS panels or newborn screening programs.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13059280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}