Human Genomics最新文献

{"title":"CLPP Gene Variants Causing Perrault Syndrome Type 3 in Han Chinese Families: A Genotype-Phenotype Study.","authors":"Xicui Long, Bingqian Yang, Wei Wang, Wan Peng, Xiaolu Wang, Wenyu Xiong, Man Liu, Huijun Yuan, Yu Lu","doi":"10.1186/s40246-025-00762-5","DOIUrl":"10.1186/s40246-025-00762-5","url":null,"abstract":"<p><strong>Background: </strong>Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) and primary ovarian insufficiency (POI) secondary to ovarian dysgenesis. However, the mutation spectrum of disease-causing genes for Perrault syndrome in the Chinese population remains poorly understood. In this study, we report on two Chinese families with Perrault syndrome type 3 caused by novel CLPP gene variants. We also conducted a comprehensive literature review of CLPP gene variants in Perrault syndrome type 3 to elucidate genotype-phenotype associations.</p><p><strong>Methods: </strong>Using Whole Genome Sequencing (WGS) data, two pedigrees with Perrault syndrome type 3 were ascertained in the Chinese Deafness Genetics Cohort through genotype-driven analysis. Variants were validated using Sanger sequencing and copy number quantification methods. In vitro analysis of splice site variants in the CLPP gene using the minigene assay.</p><p><strong>Results: </strong>Two Han Chinese families were ascertained: one with compound heterozygous variants (c.270 + 1G > C and c.355A > C [p. Ile119Leu]) and the other with missense variant (c.400G > C [p. Asp134His]) together with a large deletion in CLPP. In vitro minigene assays confirmed that the c.270 + 1G > C variant causes intron 2 retention and an alternative 5' splice site in exon 2, leading to protein alteration. Among 33 Perrault syndrome type 3 patients in literature, 97% (31/32) had hearing loss, 55% (16/29) neurological disease, and 71% (15/21) females had POI. Including our 4 novel variants, 21 pathogenic CLPP gene variants have been reported, with 57% (12/21) missense and 43% (9/21) truncating variants, mainly in the ATP-dependent Clp protease proteolytic subunit. Biallelic truncating or missense plus truncating genotypes showed higher rates of neurological disease (p = 0.001), but no significant difference in hearing loss incidence compared to biallelic missense genotypes was observed.</p><p><strong>Conclusion: </strong>This study highlights the challenges in diagnosing Perrault syndrome due to its genetically and clinically heterogeneity. By exploring novel variants and establishing genotype-phenotype correlations, we aim to improve the genetic diagnosis and consultation for this complex disorder.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"60"},"PeriodicalIF":3.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131994","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":"Genetic counseling in the Middle East: provider perspectives of patient attitudes and cultural challenges.","authors":"Shruti Shenbagam, Alan Taylor, Ruchi Jain, Khalid Fakhro, Fowzan Alkuraya, Ahmad Abou Tayoun","doi":"10.1186/s40246-025-00770-5","DOIUrl":"10.1186/s40246-025-00770-5","url":null,"abstract":"<p><p>Genomic advancements have led to increased utilization of genetic testing in clinical care, yet barriers to accessing genetic counseling and genomics services remain, particularly in the Middle East where inherited diseases are highly prevalent due to consanguinity. Limited knowledge of healthcare professionals' experiences in genetic counseling in the Middle East necessitates understanding their perspectives for better service improvement in the region. As a pilot, a survey of 32 healthcare professionals providing genetic counseling services in the Middle East explored provider experiences, patient attitudes and cultural/psychosocial factors related to genetic testing. Among the participants, 21 providers (65.6%), caring for patients of multiple ethnicities, including Arabs, recognised that there are unique challenges to counseling between these patient groups. Thematic data analysis identified that higher levels of consanguinity and stoic nature of the people are unique cultural considerations in the region. Language barriers and limited resources were identified as genetic counseling challenges. Overall, patients demonstrated good coping abilities with a genetic diagnosis. Eighteen responses (56%) highlighted an overall positive attitude, with increasing awareness and acceptance towards genetic testing. This study highlights the need for further research and interventions to address the unique challenges and improve genetic counseling services in the Middle East.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"59"},"PeriodicalIF":3.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110433","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":"Identification of loci associated with women's reproductive traits and exploration of a shared genetic basis with obesity.","authors":"Seong-Ah Kwon, Yoon Shin Cho","doi":"10.1186/s40246-025-00773-2","DOIUrl":"10.1186/s40246-025-00773-2","url":null,"abstract":"<p><strong>Background: </strong>The timing of menarche and menopause significantly affects women's health, with influences on cancer, cardiovascular disease, obesity, type 2 diabetes, and psychosocial problems. In addition, observational studies have reported that ages at menarche (AAM) and natural menopause (ANM) are correlated with obesity. To understand the genetic bases of these reproductive traits, we conducted a genome-wide association study (GWAS) of AAM and ANM in the Korean population. We also investigated the genetic correlation and causal relationship to explore the shared genetic architecture between reproductive traits and obesity in women.</p><p><strong>Results: </strong>Our GWA analyses of 45,608 and 21,599 adult women identified two and six genome-wide significant associations (P-value < 5 × 10^- 8) for AAM and ANM, respectively. Although most of the loci that we detected have been reported in previous studies, we have newly linked the JHY locus containing the SNP rs11605693 to AAM. Leveraging the GWAS results, we tested the shared genetic basis underlying AAM and ANM, which appear to be closely related to female hormone activity. Linkage disequilibrium score regression (LDSC) analysis did not identify a significant genetic correlation between the two traits. Our LDSC analyses indicated that AAM was inversely correlated with two obesity traits, body mass index (BMI) and waist circumference (WC). However, Mendelian randomization (MR) analyses did not provide evidence of a causal relationship between AAM and obesity traits.</p><p><strong>Conclusions: </strong>Overall, our study provides insights into the genetic architecture of women's reproductive traits and the shared genetic basis between AAM and obesity. Our MR analyses suggest that the genetic correlation between AAM and obesity traits results from the direct effects of genetic variants on both traits rather than a causal relationship between them.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"58"},"PeriodicalIF":3.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110488","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":"BAX-mediated ammonia-driven cell death: a novel prognostic and therapeutic target in clear cell renal cell carcinoma.","authors":"Xi Zhang, Zijie Yu, Lu Yin, Qiang Li, Shaohua He, Heng Li, Jian Li, Lian Sheng, Hongfei Wu, Hongqi Chen, Xiaoxu Zhu, Yang Lv","doi":"10.1186/s40246-025-00764-3","DOIUrl":"10.1186/s40246-025-00764-3","url":null,"abstract":"<p><strong>Background: </strong>ccRCC (clear cell renal cell carcinoma) is characterized by metabolic reprogramming and immunosuppression, leading to poor clinical prognosis. In recent years, ammonia-related cell death has attracted increasing attention as a novel mechanism related to tumor progression, but its role in ccRCC has not been clarified.</p><p><strong>Methods: </strong>In this study, the Ammonia-related Signature (AS) of ccRCC was constructed by integrating bioinformatics analysis and experimental verification. Multiple independent cohorts including TCGA, PMID 35,440,542 cohort, E-MTAB-1980, and GSE29609 were used to evaluate prognostic accuracy and clinical relevance, and biological functions of key ammonia related genes were explored by cell proliferation, clonal formation, migration, and invasion assays. ScRNA-seq was used to analyze interaction between AS and immune cells in ccRCC.</p><p><strong>Results: </strong>The ammonia-related prognostic model demonstrated robust predictive power in multiple datasets. The high AS group of patients with poor prognosis, and the tumor mutation load, immunosuppressive cell infiltration level and immune checkpoint molecular expression were higher. BAX was a key ammonia-related gene closely related to tumor progression, and its knockdown obviously inhibit proliferation, migration and invasion of ccRCC cells. Single-cell analysis confirmed the activation of ammonia-related signaling pathways in the tumor microenvironment, in particular revealing specific interactions between BAX-positive tumor cells and immunosuppressive cell populations.</p><p><strong>Conclusion: </strong>The ammonia-related cell death pathway, especially BAX, can be employed as a potential prognostic marker and therapeutic target for ccRCC, providing new ideas for individualized treatment strategies to overcome immunosuppression and improve clinical prognosis.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"57"},"PeriodicalIF":3.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093477","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":"Exploring potential methylation markers for ovarian cancer from cervical scraping samples.","authors":"Ju-Yin Lien, Lu Ann Hii, Po-Hsuan Su, Lin-Yu Chen, Kuo-Chang Wen, Hung-Cheng Lai, Yu-Chao Wang","doi":"10.1186/s40246-025-00763-4","DOIUrl":"10.1186/s40246-025-00763-4","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer has the highest mortality rate among gynecological cancers, making early detection crucial, as the five-year survival rate drops from 92% with early-stage diagnosis compared to 31% with late-stage diagnosis. Current diagnostic methods such as histopathological examination and detection of cancer antigen 125 and human epididymis protein 4 biomarkers are either invasive or lack specificity and sensitivity. However, the Papanicolaou (Pap) test, which is widely used for cervical cancer screening, shows the potential for detecting ovarian cancer by identifying tumor DNA in cervical scrapings. Since aberrant DNA methylation patterns are linked to cancer progression, DNA methylation offers a promising avenue for early diagnosis. Therefore, this study aimed to develop a methylation-based machine-learning model to stratify patients with ovarian cancer from the cervical scraping samples collected via Pap test.</p><p><strong>Results: </strong>Cervical scrapings were collected by gynecologists using conventional Pap smears. In total, 160 samples were collected: 95 normal, 37 benign, and 28 malignant. Methylation data were generated using the Illumina Infinium MethylationEPIC BeadChip array, which contains approximately 850,000 CpG loci. Methylation data were initially divided into training and testing sets in a 3:1 ratio comprising 120 and 40 samples, respectively. A two-step methylation-based model was trained using the training data for classification: a principal component analysis (PCA) model, consisting of 30 features, to classify samples as normal or tumor; then a gradient boosting model, containing 16 features, to further stratify tumor samples as benign or malignant. The two-step model achieved an accuracy of 0.88 and an F1-score of 0.86 on the testing data. Furthermore, an over-representation analysis was conducted to explore the functions associated with genes mapped from differentially methylated positions (DMPs) in comparisons between normal and tumor samples, as well as between benign and malignant samples. These results suggest that DMPs may be associated with olfactory transduction when comparing normal versus tumor samples, and immune regulation when comparing benign and malignant samples.</p><p><strong>Conclusions: </strong>Our two-step model shows promise for predicting ovarian cancer and suggests that cervical scrapings may be a viable alternative for sample collection during screening.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"56"},"PeriodicalIF":3.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093478","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":"On the aspiration to decode the impact of genomics on performance in power and endurance sports.","authors":"Martin Flück, Benedikt Gasser, Alain Dössegger","doi":"10.1186/s40246-025-00750-9","DOIUrl":"10.1186/s40246-025-00750-9","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"55"},"PeriodicalIF":3.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086180","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":"Targeted multi-layer analysis of PANoptosis-associated genes in the etiology of chronic kidney disease.","authors":"Tong Li, Yingyue Zhang, Xingzhi Wang, Qi Liu, Xiaofei Ma, Manshu Sui","doi":"10.1186/s40246-025-00768-z","DOIUrl":"10.1186/s40246-025-00768-z","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have examined the cellular and molecular interactions between chronic kidney disease (CKD) and PANoptosis, yet the genetic underpinnings remain unclear.</p><p><strong>Materials: </strong>Data at the summary level regarding the methylation, gene expression, and protein levels associated with PANoptosis were obtained from quantitative trait locus (QTL) studies. Genome-wide association study (GWAS) summary statistics for CKD were derived from a GWAS study, supplemented by a replication dataset from the FinnGen database. Genetic variants proximal to or within genes involved in PANoptosis, which showed robust associations with CKD, were utilized as instrumental variables. These variants were the subjected to SMR analysis to explore their causal relationship. The associations among QTLs were systematically analyzed. Additionally, a colocalization analysis was conducted to ascertain whether the signals identified corresponded to a shared genetic basis.</p><p><strong>Results: </strong>SMR and colocalization analysis revealed 28 methylation sites and 5 genes associated with CKD.Notably, cg01304814 (PRKAR2A) and cg09177106, cg15114474 (CCND1) were inversely associated with CKD risk. Integrating mQTL and eQTL data, we identified four genes (CCND1, GUCY2D, HGF, MADD) causally associated with CKD, with a positive correlation between HGF gene expression and protein levels.</p><p><strong>Conclusion: </strong>Our results provide evidence for the PANoptosis-related genes in the pathogenesis of CKD. Notably, PRKAR2A, HGF, CCND1 and MADD, emerged as potential mediators in the pathogenesis of CKD.</p><p><strong>Trial registration: </strong>Not applicable.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"53"},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964719","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 survey on mutation spectrum in Iranian patients with limb-girdle muscular dystrophies.","authors":"Sheyda Khalilian, Mohadeseh Fathi, Raheleh Tangestani, Pegah Larki, Arezou Sayad, Soudeh Ghafouri-Fard, Mohammad Miryounesi","doi":"10.1186/s40246-025-00771-4","DOIUrl":"10.1186/s40246-025-00771-4","url":null,"abstract":"<p><p>Limb-girdle muscular dystrophies (LGMD) designate diverse types of muscular dystrophies that predominantly affect proximal skeletal muscles. Although both autosomal recessive and dominant forms exist, the majority of cases are inherited in an autosomal recessive manner. Since the spectrum of genetic variants that cause this disorder is quite broad, next-generation sequencing techniques are the best diagnostic tools for LGMD. In this study, we provide an overview of mutation spectrum of LGMD-related genes in the Iranian patients using whole exome sequencing. Notably, CAPN3 and LAMA2 genes were the genes encompassing the highest frequencies of pathogenic or likely pathogenic variants in this cohort. Pathogenic and likely pathogenic variants were identified in CAPN3 gene in total of 10 cases out of 48 cases tested (20%). In addition, different variants in each of POMGNT1 and TTN genes were detected in five and four patients, respectively. Three patients had DYSF variants (6%). While the inheritance of the majority of cases was supposed to be in an autosomal recessive manner, in three cases, the disease inheritance was best explained by the dominant type (c.947 C > T variant in the DNAJB6, c.746G > A variant in the LMNA, and c.1417G > A variant in the TNPO3). The current study broadens the spectrum of LGMD-related mutations among Iranian patients and facilitates genetic counseling in the affected families.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"54"},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976862","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":"Bioinformatics analysis of circular RNAs associated with atrial fibrillation and their evaluation as predictive biomarkers.","authors":"Manman Wang, Yuanyuan Chen, Weiwei Yang, Xiangting Li, Genli Liu, Xin Wang, Shuai Liu, Ge Gao, Fanhua Meng, Feifei Kong, Dandan Sun, Wei Qin, Bo Dong, Jinguo Zhang","doi":"10.1186/s40246-025-00760-7","DOIUrl":"10.1186/s40246-025-00760-7","url":null,"abstract":"<p><strong>Background: </strong>Circular noncoding RNAs (circRNAs) are implicated in many human diseases, but their role in atrial fibrillation (AF) is poorly understood. In this study, we performed bioinformatics analysis of circRNA sequencing data to identify AF-related circRNAs.</p><p><strong>Methods: </strong>Left atrial appendage (LAA) samples were obtained from patients with valvular heart disease and were categorised into the sinus rhythm (SR; n = 4) and AF (n = 4) groups. CircRNA sequencing analysis was performed to identify differentially expressed (DE) circRNAs in AF patients. Functional enrichment analysis of DE circRNAs was performed to identify enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.</p><p><strong>Results: </strong>We identified 3338 DE circRNAs, including 2147 upregulated and 1191 downregulated circRNAs, in AF patients. A ceRNA network of 16 DE circRNAs, 11 DE miRNAs, and 15 DE mRNAs was constructed. Functional enrichment analyses revealed that the AF-related DE circRNAs were enriched in response to vitamin D, the potassium channel complex, delayed rectifier potassium channel activity, osteoclast differentiation, primary immunodeficiency, endocrine and other factor-regulated calcium reabsorption and other processes. ROC curve analysis identified circRNA_00324, circRNA_17225, circRNA_16305, circRNA_10233, circRNA_05499, circRNA_03183, circRNA_14211, and circRNA_18422 as potential predictive biomarkers for distinguishing AF patients from SR patients, with AUC values of 0.9138, 0.7370, 0.8526, 0.6803, 0.8163, 0.8662, 0.7664, and 0.9320, respectively.</p><p><strong>Conclusions: </strong>In this study, we constructed an AF-related ceRNA network and identified eight circRNAs as potential predictive biomarkers of AF.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"52"},"PeriodicalIF":3.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998116","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":"Prognostic significance of clonal hematopoiesis in STEMI: a 10-year follow-up reveals high-risk gene mutations.","authors":"Wen-Lang Fan, Jih-Kai Yeh, Li-Ching Hsieh, Ming-Lung Tsai, Ming-Yun Ho, Yi-Chun Huang, I-Chang Hsieh, Ming-Shien Wen, Chao-Yung Wang","doi":"10.1186/s40246-025-00757-2","DOIUrl":"10.1186/s40246-025-00757-2","url":null,"abstract":"<p><strong>Background: </strong>To elucidate the extent and clinical implications of clonal hematopoiesis of indeterminate potential (CHIP) prevalence in patients with ST-segment elevation myocardial infarction (STEMI), and to evaluate its utility as a contributory factor for risk stratification in long-term outcomes.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed in a cohort of 101 patients presenting with STEMI who underwent emergency percutaneous coronary intervention. These patients were longitudinally followed for over 120 months. Their genomic data were compared with those from a control group of 706 individuals without cardiovascular events. Comparative analyses were conducted to identify patterns of CHIP between the STEMI and control cohorts.</p><p><strong>Results: </strong>In our cohort, 37.6% (n = 38) of STEMI patients exhibited somatic mutations associated with CHIP at a variant allele frequency of 1% or greater, compared to 22.8% (n = 161) in the control group. The most frequently detected mutations in STEMI patients were in the ASXL1 and CREBBP genes, each present in 5.0% of this cohort. Long-term follow-up revealed that STEMI patients with CHIP had a higher incidence of major adverse cardiovascular events (MACEs), with an adjusted hazard ratio of 2.23 (95% confidence interval (CI) 1.16-4.28, p = 0.015).</p><p><strong>Conclusion: </strong>CHIP is prevalent in the STEMI patient cohort and is significantly correlated with adverse clinical outcomes. Incorporating CHIP status could enhance the risk stratification process, thus informing more tailored clinical management strategies for STEMI patients.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"51"},"PeriodicalIF":3.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978088","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}