Human Genetics最新文献

{"title":"Rare homozygous cilia gene variants identified in consanguineous congenital heart disease patients.","authors":"Daniel A Baird, Hira Mubeen, Canan Doganli, Jasmijn B Miltenburg, Oskar Kaaber Thomsen, Zafar Ali, Tahir Naveed, Asif Ur Rehman, Shahid Mahmood Baig, Søren Tvorup Christensen, Muhammad Farooq, Lars Allan Larsen","doi":"10.1007/s00439-024-02703-z","DOIUrl":"10.1007/s00439-024-02703-z","url":null,"abstract":"<p><p>Congenital heart defects (CHD) appear in almost one percent of live births. Asian countries have the highest birth prevalence of CHD in the world. Recessive genotypes may represent a CHD risk factor in Asian populations with a high degree of consanguineous marriages. Genetic analysis of consanguineous families may represent a relatively unexplored source for investigating CHD etiology. To obtain insight into the contribution of recessive genotypes in CHD we analysed a cohort of forty-nine Pakistani CHD probands, originating from consanguineous unions. The majority (82%) of patient's malformations were septal defects. We identified protein altering, rare homozygous variants (RHVs) in the patient's coding genome by whole exome sequencing. The patients had a median of seven damaging RHVs each, and our analysis revealed a total of 758 RHVs in 693 different genes. By prioritizing these genes based on variant severity, loss-of-function intolerance and specific expression in the developing heart, we identified a set of 23 candidate disease genes. These candidate genes were significantly enriched for genes known to cause heart defects in recessive mouse models (P < 2.4e-06). In addition, we found a significant enrichment of cilia genes in both the initial set of 693 genes (P < 5.4e-04) and the 23 candidate disease genes (P < 5.2e-04). Functional investigation of ADCY6 in cell- and zebrafish-models verified its role in heart development. Our results confirm a significant role for cilia genes in recessive forms of CHD and suggest important functions of cilia genes in cardiac septation.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1323-1339"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodologies underpinning polygenic risk scores estimation: a comprehensive overview.","authors":"Carene Anne Alene Ndong Sima, Kathryn Step, Yolandi Swart, Haiko Schurz, Caitlin Uren, Marlo Möller","doi":"10.1007/s00439-024-02710-0","DOIUrl":"10.1007/s00439-024-02710-0","url":null,"abstract":"<p><p>Polygenic risk scores (PRS) have emerged as a promising tool for predicting disease risk and treatment outcomes using genomic data. Thousands of genome-wide association studies (GWAS), primarily involving populations of European ancestry, have supported the development of PRS models. However, these models have not been adequately evaluated in non-European populations, raising concerns about their clinical validity and predictive power across diverse groups. Addressing this issue requires developing novel risk prediction frameworks that leverage genetic characteristics across diverse populations, considering host-microbiome interactions and a broad range of health measures. One of the key aspects in evaluating PRS is understanding the strengths and limitations of various methods for constructing them. In this review, we analyze strengths and limitations of different methods for constructing PRS, including traditional weighted approaches and new methods such as Bayesian and Frequentist penalized regression approaches. Finally, we summarize recent advances in PRS calculation methods development, and highlight key areas for future research, including development of models robust across diverse populations by underlining the complex interplay between genetic variants across diverse ancestral backgrounds in disease risk as well as treatment response prediction. PRS hold great promise for improving disease risk prediction and personalized medicine; therefore, their implementation must be guided by careful consideration of their limitations, biases, and ethical implications to ensure that they are used in a fair, equitable, and responsible manner.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1265-1280"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic and phenotypic correlations in tooth agenesis: insights from WNT10A and EDA mutations in syndromic and non-syndromic forms.","authors":"Youmei Wu, Ling Lai, Junyang Chen, Xinzhu Li, Jin Hou","doi":"10.1007/s00439-024-02705-x","DOIUrl":"10.1007/s00439-024-02705-x","url":null,"abstract":"<p><p>Tooth agenesis (TA) occurs when tooth development is disrupted at the initiation stage. It can be classified into non-syndromic and syndromic forms (named NSTA and STA), depending on whether it is accompanied by abnormalities of other organs and systems. Genetic factors play a predominant role in the pathogenesis of tooth agenesis, with dozens of genes implicated in both forms. Several genes have been identified, mutations in which can lead to both forms of TA. Among these, WNT10A and EDA are frequently mutated genes in this context, representing extensively researched and documented genes in human non-syndromic selective agenesis of permanent teeth and their association with ectodermal dysplasia syndromes. In this review, we present an overview of the current knowledge regarding genes associated with NSTA and STA, focusing on the distribution and nature of WNT10A and EDA gene mutations. We also explore how these mutations relate to the condition's both forms, including their association with the number of missing permanent teeth.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1253-1264"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative genomic analyses identify neuroblastoma risk genes involved in neuronal differentiation.","authors":"Matilde Tirelli, Ferdinando Bonfiglio, Sueva Cantalupo, Annalaura Montella, Marianna Avitabile, Teresa Maiorino, Sharon J Diskin, Achille Iolascon, Mario Capasso","doi":"10.1007/s00439-024-02700-2","DOIUrl":"10.1007/s00439-024-02700-2","url":null,"abstract":"<p><p>Genome-Wide Association Studies (GWAS) have been decisive in elucidating the genetic predisposition of neuroblastoma (NB). The majority of genetic variants identified in GWAS are found in non-coding regions, suggesting that they can be causative of pathogenic dysregulations of gene expression. Nonetheless, pinpointing the potential causal genes within implicated genetic loci remains a major challenge. In this study, we integrated NB GWAS and expression Quantitative Trait Loci (eQTL) data from adrenal gland to identify candidate genes impacting NB susceptibility. We found that ZMYM1, CBL, GSKIP and WDR81 expression was dysregulated by NB predisposing variants. We further investigated the functional role of the identified genes through computational analysis of RNA sequencing (RNA-seq) data from single-cell and whole-tissue samples of NB, neural crest, and adrenal gland tissues, as well as through in vitro differentiation assays in NB cell cultures. Our results indicate that dysregulation of ZMYM1, CBL, GSKIP, WDR81 may lead to malignant transformation by affecting early and late stages of normal program of neuronal differentiation. Our findings enhance the understanding of how specific genes contribute to NB pathogenesis by highlighting their influence on neuronal differentiation and emphasizing the impact of genetic risk variants on the regulation of genes involved in critical biological processes.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1293-1309"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biallelic variants in ERLIN1: a series of 13 individuals with spastic paraparesis.","authors":"Guillaume Cogan, Maha S Zaki, Mahmoud Issa, Boris Keren, Marine Guillaud-Bataille, Florence Renaldo, Arnaud Isapof, Pauline Lallemant, Giovanni Stevanin, Lena Guillot-Noel, Thomas Courtin, Julien Buratti, Cécile Freihuber, Joseph G Gleeson, Robyn Howarth, Alexandra Durr, Jean-Madeleine de Sainte Agathe, Cyril Mignot","doi":"10.1007/s00439-024-02702-0","DOIUrl":"10.1007/s00439-024-02702-0","url":null,"abstract":"<p><p>Biallelic variants in the ERLIN1 gene were recently reported as the cause of two motor neuron degeneration diseases, SPG62 and a recessive form of amyotrophic lateral sclerosis. However, only 12 individuals from five pedigrees have been identified so far. Thus, the description of the disease remains limited. Following the discovery of a homozygous pathogenic variant in a girl with SPG62, presenting with intellectual disability, and epilepsy, we gathered the largest series of SPG62 cases reported so far (13 individuals) to better understand the phenotype associated with ERLIN1. We collected molecular and clinical data for 13 individuals from six families with ERLIN1 biallelic variants. We performed RNA-seq analyses to characterize intronic variants and used Alphafold and a transcripts database to characterize the molecular consequences of the variants. We identified three new variants suspected to alter the bell-shaped ring formed by the ERLIN1/ERLIN2 complex. Affected individuals had childhood-onset paraparesis with slow progression. Six individuals presented with gait ataxia and three had superficial sensory loss. Aside from our proband, none had intellectual disability or epilepsy. Biallelic pathogenic ERLIN1 variants induce a rare, predominantly pure, spastic paraparesis, with possible cerebellar and peripheral nerve involvement.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1353-1362"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide study of gene-by-sex interactions identifies risks for cleft palate.","authors":"Kelsey Robinson, Randy Parrish, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, Lord J J Gowans, Jacqueline T Hecht, Lina Moreno Uribe, Jeffrey C Murray, Gary M Shaw, Seth M Weinberg, Harrison Brand, Mary L Marazita, David J Cutler, Michael P Epstein, Jingjing Yang, Elizabeth J Leslie","doi":"10.1007/s00439-024-02704-y","DOIUrl":"10.1007/s00439-024-02704-y","url":null,"abstract":"<p><p>Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP. CL/P is more common in males and CP is more frequently observed in females, so we hypothesized there would also be sex-specific differences for CP. Using a trio-based cohort, we performed sex-stratified genome-wide association studies (GWAS) based on proband sex followed by a genome-wide gene-by-sex (G × S) interaction testing. There were 13 loci significant for G × S interactions, with the top finding in LTBP1 (RR = 3.37 [2.04-5.56], p = 1.93 × 10^-6). LTBP1 plays a role in regulating TGF-β bioavailability, and knockdown in both mice and zebrafish lead to craniofacial anomalies. Further, there is evidence for differential expression of LTBP1 between males and females in both mice and humans. Therefore, we tested the association between the imputed genetically regulated gene expression of genes with significant G × S interactions and the CP phenotype. We found significant association for LTBP1 in cell cultured fibroblasts in female probands (p = 0.0013) but not in males. Taken altogether, we show there are sex-specific risks for CP that are otherwise undetectable in a combined sex cohort, and LTBP1 is a candidate risk gene, particularly in females.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1341-1352"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exome variant prioritization in a large cohort of hearing-impaired individuals indicates IKZF2 to be associated with non-syndromic hearing loss and guides future research of unsolved cases.","authors":"Hedwig M Velde, Maryam Vaseghi-Shanjani, Jeroen J Smits, Gayatri Ramakrishnan, Jaap Oostrik, Mieke Wesdorp, Galuh Astuti, Helger G Yntema, Lies Hoefsloot, Cris P Lanting, Martijn A Huynen, Anna Lehman, Stuart E Turvey, Ronald J E Pennings, Hannie Kremer","doi":"10.1007/s00439-024-02706-w","DOIUrl":"10.1007/s00439-024-02706-w","url":null,"abstract":"<p><p>Although more than 140 genes have been associated with non-syndromic hereditary hearing loss (HL), at least half of the cases remain unexplained in medical genetic testing. One reason is that pathogenic variants are located in 'novel' deafness genes. A variant prioritization approach was used to identify novel (candidate) genes for HL. Exome-wide sequencing data were assessed for subjects with presumed hereditary HL that remained unexplained in medical genetic testing by gene-panel analysis. Cases in group AD had presumed autosomal dominantly inherited HL (n = 124), and in group AR, presumed autosomal recessive HL (n = 337). Variants in known and candidate deafness genes were prioritized based on allele frequencies and predicted effects. Selected variants were tested for their co-segregation with HL. Two cases were solved by variants in recently identified deafness genes (ABHD12, TRRAP). Variant prioritization also revealed potentially causative variants in candidate genes associated with recessive and X-linked HL. Importantly, missense variants in IKZF2 were found to co-segregate with dominantly inherited non-syndromic HL in three families. These variants specifically affected Zn²⁺-coordinating cysteine or histidine residues of the zinc finger motifs 2 and 3 of the encoded protein Helios. This finding indicates a complex genotype-phenotype correlation for IKZF2 defects, as this gene was previously associated with non-syndromic dysfunction of the immune system and ICHAD syndrome, including HL. The designed strategy for variant prioritization revealed that IKZF2 variants can underlie non-syndromic HL. The large number of candidate genes for HL and variants therein stress the importance of inclusion of family members for variant prioritization.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1379-1399"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R2ROC: an efficient method of comparing two or more correlated AUC from out-of-sample prediction using polygenic scores.","authors":"Md Moksedul Momin, Naomi R Wray, S Hong Lee","doi":"10.1007/s00439-024-02682-1","DOIUrl":"10.1007/s00439-024-02682-1","url":null,"abstract":"<p><p>Polygenic risk scores (PRSs) enable early prediction of disease risk. Evaluating PRS performance for binary traits commonly relies on the area under the receiver operating characteristic curve (AUC). However, the widely used DeLong's method for comparative significance tests suffer from limitations, including computational time and the lack of a one-to-one mapping between test statistics based on AUC and <math><msup><mi>R</mi> <mn>2</mn></msup> </math> . To overcome these limitations, we propose a novel approach that leverages the Delta method to derive the variance and covariance of AUC values, enabling a comprehensive and efficient comparative significance test. Our approach offers notable advantages over DeLong's method, including reduced computation time (up to 150-fold), making it suitable for large-scale analyses and ideal for integration into machine learning frameworks. Furthermore, our method allows for a direct one-to-one mapping between AUC and <math><msup><mi>R</mi> <mn>2</mn></msup> </math> values for comparative significance tests, providing enhanced insights into the relationship between these measures and facilitating their interpretation. We validated our proposed approach through simulations and applied it to real data comparing PRSs for diabetes and coronary artery disease (CAD) prediction in a cohort of 28,880 European individuals. The PRSs were derived using genome-wide association study summary statistics from two distinct sources. Our approach enabled a comprehensive and informative comparison of the PRSs, shedding light on their respective predictive abilities for diabetes and CAD. This advancement contributes to the assessment of genetic risk factors and personalized disease prediction, supporting better healthcare decision-making.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1193-1205"},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide assessment of shared genetic landscape of idiopathic pulmonary fibrosis and its comorbidities.","authors":"Yuanhao Yang, Yong H Sheng, Patricia Carreira, Tong Wang, Huiying Zhao, Ran Wang","doi":"10.1007/s00439-024-02696-9","DOIUrl":"10.1007/s00439-024-02696-9","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease accompanied by both local and systemic comorbidities. Genetic factors play a role in the development of IPF and certain associated comorbidities. Nevertheless, it is uncertain whether there are shared genetic factors underlying IPF and these comorbidities. To bridge this knowledge gap, we conducted a systematic investigation into the shared genetic architecture between IPF and ten prevalent heritable comorbidities (i.e., body mass index [BMI], coronary artery disease [CAD], chronic obstructive pulmonary disease [COPD], gastroesophageal reflux disease, lung cancer, major depressive disorder [MDD], obstructive sleep apnoea, pulmonary hypertension [PH], stroke, and type 2 diabetes), by utilizing large-scale summary data from their respective genome-wide association studies and multi-omics studies. We revealed significant (false discovery rate [FDR] < 0.05) and moderate genetic correlations between IPF and seven comorbidities, excluding lung cancer, MDD and PH. Evidence suggested a partially putative causal effect of IPF on CAD. Notably, we observed FDR-significant genetic enrichments in lung for the cross-trait between IPF and CAD and in liver for the cross-trait between IPF and COPD. Additionally, we identified 65 FDR-significant genes over-represented in 20 biological pathways related to the etiology of IPF, BMI, and COPD, including inflammation-related mucin gene clusters. Several of these genes were associated with clinically relevant drugs for the treatment of IPF, CAD, and/or COPD. Our results underscore the pervasive shared genetic basis between IPF and its common comorbidities and hold future implications for early diagnosis of IPF-related comorbidities, drug repurposing, and the development of novel therapies for IPF.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1223-1239"},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma-derived exosomal miRNA profiles reveal potential epigenetic pathogenesis of premature ovarian failure.","authors":"Jiaqiong Lin, Zhihong Wu, Yingchun Zheng, Zongrui Shen, Zhongzhi Gan, Shunfei Ma, Yanhui Liu, Fu Xiong","doi":"10.1007/s00439-023-02618-1","DOIUrl":"10.1007/s00439-023-02618-1","url":null,"abstract":"<p><p>The role of plasma-derived exosomal miRNA in premature ovarian failure (POF) remains unclear. This study aimed to investigate the epigenetic pathogenesis of POF through exosomal miRNA sequencing. Exosomes were isolated and characterized from six POF patients and four healthy individuals using nanoparticle tracking analysis, transmission electron microscopy and western blot analysis. Exosomal miRNA sequencing was performed to identify differentially expressed miRNAs with |fold change| greater than 1.5 and p value less than 0.05. Bioinformatics analysis in GSE39501 dataset and our sequencing data was conducted to investigate underlying mechanisms of POF. The functional role of hsa-miR-19b-3p was assessed using CCK8, western blot, flow cytometry and fluorescence staining. The regulatory effect of hsa-miR-19b-3p on BMPR2 was investigated through miRNA transfection, qPCR analysis, and luciferase reporter assay. Statistical significance was determined using t-tests and one-way ANOVA (p < 0.05). Exosomal miRNA sequencing revealed 18 dysregulated miRNAs in POF patients compared to healthy controls. Functional enrichment analysis demonstrated their involvement in cell growth, oocyte meiosis and PI3K-Akt signaling pathways. Moreover, the constructed miRNA-mRNA network unveiled potential regulatory mechanisms underlying POF, particularly implicating hsa-miR-19b-3p in the regulation of BMPR2. In vitro assays conducted on KGN cells confirmed that hsa-miR-19b-3p promoted apoptosis, as evidenced by reduced cell viability, decayed mitochondrial membrane potential and increased apoptotic rate, thereby supporting its role in POF. Notably, hsa-miR-19b-3p was found to significantly downregulate BMPR2 expression via targeting its 3'UTR, while co-expression analysis revealed strong associations between BMPR2 and POF-related processes. This study sheds light on the epigenetic pathogenesis of POF by investigating exosomal miRNA profiles. Particularly, hsa-miR-19b-3p emerged as a potential regulator of BMPR2 and demonstrated its functional significance in POF through modulation of apoptosis.</p>","PeriodicalId":13175,"journal":{"name":"Human Genetics","volume":" ","pages":"1021-1034"},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}