Human Genomics最新文献

{"title":"Pharmacogenomic insights into atorvastatin and rosuvastatin adverse effects: a prospective observational study in the UAE's multiethnic population.","authors":"Mais N Alqasrawi, Zeina N Al-Mahayri, Areej S AlBawa'neh, Lubna Q Khasawneh, Lilas Dabaghie, Sahar M Altoum, Dana Hamza, Virendra Misra, Husam Ouda, Salahdein Aburuz, Fatima Al-Maskari, Juma AlKaabi, George P Patrinos, Bassam R Ali","doi":"10.1186/s40246-025-00753-6","DOIUrl":"https://doi.org/10.1186/s40246-025-00753-6","url":null,"abstract":"<p><strong>Background: </strong>Statins are essential for managing cardiovascular disease (CVD), but adverse effects often lead to treatment discontinuation and non-adherence, underscoring the need for personalized approaches. This study aimed to evaluate the influence of pharmacogenomic (PGx) variants and demographic factors on statin-associated adverse effects in a multiethnic cohort from the United Arab Emirates (UAE).</p><p><strong>Methods: </strong>This sub-analysis of the EmHeart Study included 675 patients using rosuvastatin or atorvastatin. Patients were genotyped for SLCO1B1 and ABCG2 actionable variants using real-time PCR. Data on demographics, comorbidities, and statin use were extracted from electronic health records. Adverse events, including statin-associated muscle symptoms (SAMS) and liver enzyme elevation, were tracked over 12 months. Associations were analyzed using chi-square tests and logistic regression.</p><p><strong>Results: </strong>Rosuvastatin users carrying the ABCG2 rs2231142 variant had a threefold increased risk of liver enzyme elevation, particularly among East Asian patients (P < 0.005). Atorvastatin users with the SLCO1B1 rs4149056 variant exhibited a twofold increased risk of SAMS, with higher rates observed in females and Arabs (P < 0.05). The combination of rosuvastatin with ezetimibe further exacerbated risks of SAMS and liver enzyme elevation.</p><p><strong>Conclusion: </strong>This study highlights the importance of genetic testing and demographic factors, such as ethnicity and gender, in tailoring statin therapy to minimize adverse effects. Despite extensive research on PGx-guided statin prescribing, clinical implementation remains limited. Integrating PGx testing into routine practice and enhancing physician awareness of genetic and demographic risk factors can improve the safety, efficacy, and adherence of lipid-lowering therapies in diverse populations.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"44"},"PeriodicalIF":3.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965084","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":"Assessing the causal effects of type 2 diabetes and obesity-related traits on COVID-19 severity.","authors":"Jieun Seo, Gaeun Kim, Seunghwan Park, Aeyeon Lee, Liming Liang, Taesung Park, Wonil Chung","doi":"10.1186/s40246-025-00747-4","DOIUrl":"https://doi.org/10.1186/s40246-025-00747-4","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) and obesity-related traits are highly comorbid with coronavirus disease 2019 (COVID-19), but their causal relationships with disease severity remain unclear. While recent Mendelian randomization (MR) studies suggest a causal link between obesity-related traits and COVID-19 severity, findings regarding T2D are inconsistent, particularly when adjusting for body mass index (BMI). This study aims to clarify these relationships.</p><p><strong>Methods: </strong>We applied various MR methods to assess the causal effects of BMI-adjusted T2D (T2DadjBMI) and obesity-related traits (BMI, waist circumference, and waist-hip ratio) on COVID-19 severity. Genetic instruments were obtained from large-scale genome-wide association studies (GWAS), including 898K participants for T2D and 2M for COVID-19 severity. To address potential bias from sample overlap, we conducted large-scale simulations comparing MR results from overlapping and independent samples.</p><p><strong>Results: </strong>Our MR analysis identified a significant causal relationship between T2DadjBMI and increased COVID-19 severity (OR = 1.057, 95% CI = 1.012-1.105). Obesity-related traits were also causally associated with COVID-19 severity. Simulations confirmed that MR results remained robust to sample overlap, demonstrating consistency between overlapping and independent datasets.</p><p><strong>Conclusions: </strong>These findings highlight the causal role of T2D and obesity-related traits in COVID-19 severity, emphasizing the need for targeted prevention and management strategies for high-risk populations. The robustness of our MR analysis, even in the presence of sample overlap, strengthens the reliability of these causal inferences.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"43"},"PeriodicalIF":3.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984574","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":"Molecular genetic testing and cohort analysis of 32 twin pairs with neurodevelopmental disorders-Reporting a novel de novo variant of TET3.","authors":"Lianni Mei, Chunchun Hu, Guangbo Jin, Chuanhui Ge, Yiting Zhu, Dongyun Li, Wenzhu Peng, Huiping Li, Xiu Xu, Yan Jiang, Guoliang Xu, Qiong Xu","doi":"10.1186/s40246-025-00748-3","DOIUrl":"https://doi.org/10.1186/s40246-025-00748-3","url":null,"abstract":"<p><p>Neurodevelopmental disorders (NDDs) pose significant challenges due to their impact on cognitive, social and motor abilities, often rooted in genetic factors such as copy number variations (CNVs) and single nucleotide variantions (SNVs). Molecular genetic testing, advanced due to sequencing technologies, is instrumental in diagnosing NDDs, with twins offering unique perspectives in detecting novel de novo CNVs and SNVs. The study enrolled 32 pairs of twins that underwent molecular genetic testing and comprehensive clinical data collection. Additionally, we analyzed the potential deleterious effects of a novel de novo TET methylcytosine dioxygenase 3 (TET3) variant (c.4927G > A) using western blotting, immunofluorescence assay and enzymatic activity assay. Analyzing simultaneously, the overall detection yield of molecular genetic testing was 17.2% (11/64). Children with disease-related genetic variants had lower total developmental quotients (DQ) than children without disease-related genetic variants. One pair of monozygotic twins carried a novel de novo TET3 variant. Immunostaining assay revealed that while the wildtype TET3 protein was evenly distributed in the nucleus, the variant was concentrated around the nucleus. Anenzymatic assay using corresponding TET2 mutants suggested that the variant has a significantly reduced activity. Taken together, our study elaborated molecular genetic testing results of 32 pairs of twins and found that children with lower developmental levels are prone to possessing identifiable genetic variants. We reported the clinical phenotype of a pair of monozygotic twins carrying a novel de novo TET3 variant and confirmed the detrimental effects of this variant in vitro.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"42"},"PeriodicalIF":3.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968270","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":"Functional analysis of a novel FOXL2 mutation in blepharophimosis, ptosis, and epicanthus inversus syndrome type II and elucidation of the genotype-phenotype correlation.","authors":"Bingyan Shen, Xi Chen, Xiuying Zhu, Ziwen Chen, Yenan Fang, Qin Dai, Xinyu Li, Qiqi Xie, Wencan Wu, Min Wang","doi":"10.1186/s40246-025-00752-7","DOIUrl":"https://doi.org/10.1186/s40246-025-00752-7","url":null,"abstract":"<p><strong>Background: </strong>Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare autosomal dominant disorder caused by genetic mutations. However, the genotype-phenotype correlation remains unclear. This study aimed to identify mutations in a Chinese family with BPES and elucidate the genotype-phenotype relationship.</p><p><strong>Methods: </strong>A comprehensive clinical and molecular genetic analysis was conducted on a three-generation Chinese family with BPES, which was prospectively enrolled at the Eye Hospital of Wenzhou Medical University. Affected individuals underwent systematic phenotyping, including detailed physical and ophthalmic evaluations. Genomic DNA was isolated from peripheral blood samples and subjected to whole-exome sequencing, followed by targeted Sanger sequencing for variant validation. Candidate disease-associated variants were analyzed using in silico predictive algorithms to assess their potential structural and functional impact on encoded proteins. To further elucidate the pathogenicity of the identified mutation, functional studies were performed, including immunofluorescence-based subcellular localization assays and quantitative real-time PCR to evaluate transcriptional regulatory effects.</p><p><strong>Results: </strong>Six affected individuals of this pedigree presented with canonical BPES features including small palpebral fissures, ptosis, epicanthus inversus, and telecanthus, without premature ovarian failure, consistent with a diagnosis of BPES type II. Whole-exome sequencing revealed a heterozygous missense mutation (c.313 A > C:p.N105H) in FOXL2, which was subsequently validated by Sanger sequencing. This variant demonstrated complete cosegregation with the BPES phenotype across all affected family members. According to ACMG guidelines, the variant was classified as Likely Pathogenic (PS1 + PM1 + PM2 + PP3). In silico pathogenicity prediction tools classified the p.N105H variant as deleterious. Immunofluorescence assays revealed aberrant nuclear aggregation of the mutant FOXL2 protein, and functional characterization via quantitative real-time PCR demonstrated no significant dysregulation (P > 0.05) of downstream targets (STAR, OSR2).</p><p><strong>Conclusions: </strong>This study provides functional evidence of the pathogenic FOXL2 mutation (c.313 A > C, p.N105H) in BPES type II, demonstrating its disruptive effects on protein localization while maintaining normal transcriptional activity of downstream targets. These findings expand the mutational spectrum of FOXL2 related disorders and enhance our understanding of genotype-phenotype correlations in BPES.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"41"},"PeriodicalIF":3.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965071","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":"Genomics and athletic performance: an emerging discipline that is not yet ready for society.","authors":"Aikaterini Psatha, Christina Mitropoulou, George P Patrinos","doi":"10.1186/s40246-025-00751-8","DOIUrl":"https://doi.org/10.1186/s40246-025-00751-8","url":null,"abstract":"<p><p>Genomics of athletic performance is an emerging discipline with a high degree of controversy. With the existing level of evidence, it is both premature and highly risky to exploit current human genomics knowledge to predict exercise and sports performance or enhance existing training methodologies. Until more solid evidence on the influence of genomic variants in athletic performance becomes available, accompanied by regulatory approved genome-guided recommendations, all genetic associations should be restricted from general public access as commercial services, since genomic markers cannot per se predict athletic performance for talent identification, resistance to injuries or the ability to recover from them. Evidently, the complex interplay of genetics with other physical, physiological and even psychological and mental characteristics to produce a world-class athlete is still not understood.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"40"},"PeriodicalIF":3.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012254","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":"Comprehensive analysis of prognosis markers with molecular features derived from pan-cancer whole-genome sequences.","authors":"Mamoru Kato, Jo Nishino, Momoko Nagai, Hirofumi Rokutan, Daichi Narushima, Hanako Ono, Takanori Hasegawa, Seiya Imoto, Shigeyuki Matsui, Tatsuhiko Tsunoda, Tatsuhiro Shibata","doi":"10.1186/s40246-025-00744-7","DOIUrl":"https://doi.org/10.1186/s40246-025-00744-7","url":null,"abstract":"<p><p>Cancer prognosis markers are useful for treatment decisions; however, the omics-level landscape is not well understood across multiple cancer types. Pan-Cancer Analysis of Whole Genomes (PCAWG) provides unprecedented access to various types of molecular data, ranging from typical DNA mutations and RNA expressions to more deeply analyzed or whole-genomic features, such as HLA haplotypes and structural variations. We analyzed the PCAWG data of 13 cancer types from 1,514 patients to identify prognosis markers belonging to 17 molecular features in the survival analysis based on the Cox and Lasso regression methods. We found that germline features including HLA haplotypes, neoantigens, and the number of structural variations were associated with overall survival; however, mutational signatures were not. Measuring a few markers provided a sufficient prognostic performance evaluated by c-index for each cancer type. DNA markers demonstrated better or comparable prognostic performance compared to RNA markers in some cancer types. \"Universal\" markers strongly associated with overall survival across cancer types were not identified. These findings will give insights into the clinical implementation of prognosis markers.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"39"},"PeriodicalIF":3.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017472","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":"Reliability of clinical impressions and optimal genetic diagnostic strategies of heritable connective tissue disorders with ocular involvement in a large Chinese cohort.","authors":"Qin-Meng Shu, Yu-Qiao Ju, Yuan Zong, Ting Zhang, Xin Huang, Feng-Juan Gao, Qing Chang","doi":"10.1186/s40246-025-00749-2","DOIUrl":"10.1186/s40246-025-00749-2","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate the reliability of clinical impressions based on ocular manifestations in patients suspected of heritable connective tissue disorders (HCTDs) compared to the final genetic diagnosis. Furthermore, it sought to determine the optimal diagnostic strategy for patients with HCTDs through pathogenicity analysis.</p><p><strong>Methods: </strong>Clinical characteristics of 58 patients suspected of HCTDs were analyzed to establish provisional clinical diagnoses. Subsequently, next-generation sequence and Sanger sequence was performed to obtain genetic diagnoses. Pathogenicity of identified variants was assessed through conservation analysis and the functional impact, which was predicted using three-dimensional protein structure modeling.</p><p><strong>Results: </strong>The provisional clinical diagnosis was concordant with the molecular diagnostic result in only 21 patients. Independent of the initial clinical impression, a probable genetic diagnosis was achieved for all 58 patients following comprehensive re-analysis of next-generation sequence data, combined with pathogenicity assessment using three-dimensional protein structure and conservation analysis of suspicious positive variants.</p><p><strong>Conclusion: </strong>This study broadens the mutational spectrum of HCTDs with 31 novel variants. By employing innovative methodologies to delineate phenotype-genotype relationships, including the detection of potentially pathogenic variants, this work may inform future diagnostic strategies and guide comprehensive disease and organ system monitoring. Ongoing refinement and vigilant clinical oversight remain essential for patients and their families.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"38"},"PeriodicalIF":3.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811395","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":"Clinical utility of trio whole exome sequencing in fetuses with ultrasound anomalies.","authors":"Ziye Zeng, Lan Zhang, Yuqin Zhou, Xue Zhang, Hong Yi, He Li, Yuqi Liu, Jian Li, Qian Chen, Yulin Chen, Guiming Yu, Jing Yi, Yana Zhang, Hua Zhang, Yanling Dong","doi":"10.1186/s40246-025-00745-6","DOIUrl":"10.1186/s40246-025-00745-6","url":null,"abstract":"<p><strong>Introduction: </strong>Ultrasound scanning anomalies in fetuses are a cause for concern and often necessitate further diagnostic procedures. This retrospective study evaluated the utility of trio whole exome sequencing (trio-WES) in the diagnosis of fetuses with ultrasound anomalies.</p><p><strong>Methods: </strong>We included fetuses diagnosed with fetal ultrasound anomalies referred to the First Affiliated Hospital of Chongqing Medical University between November 2018 and July 2023. Fetal anomalies were classified into structural anomalies, dynamic anomalies, and soft markers. Karyotype analysis, chromosomal microarray analysis (CMA) or copy number variation sequencing (CNV-seq) and trio-WES were performed for the eligible cases. Perinatal outcomes were recorded and evaluated at postnatal follow-up.</p><p><strong>Results: </strong>A total of 316 fetuses were included for the analysis, including 199 (63.0%) cases with structural abnormalities, 63 (19.9%) cases with dynamic abnormalities, and 54 (17.1%) fetuses with ultrasonic soft markers. The diagnostic yield of karyotyping and CMA/CNV-seq was 4.1% (13/316), and Trio-WES achieved an additional diagnosis rate of 15.8% (50/316). Pathogenic or likely pathogenic alleles (P/LP) variants of 132 genes were identified in 125 (39.6%, 125/316) cases, and variant of uncertain significance (VUS) was detected in 81 samples (25.6%, 81/316). Ten cases (3.2%, 10/316,) were found to have pathogenic karyotype or CNVs in supplementary analysis of WES. Fetuses presenting musculoskeletal anomalies and multiple anomalies demonstrated highest diagnostic rates at 36.4% (8/22) and 36.1% (13/36), respectively. The diagnostic rate of fetuses with short femur was 20% (8/40), significantly higher than other ultrasonic soft markers. The modes of inheritance observed in patients with molecular diagnoses were autosomal dominant (AD) in 66.0% cases (33/50), autosomal recessive (AR) in 26.0% cases (13/50), and X-linked (XL) in 8.0% cases (4/50).</p><p><strong>Conclusion: </strong>The integration of CMA/CNV-seq with trio-WES, alongside prenatal ultrasound scanning, holds the promise of significantly enriching our ability to decipher fetal phenotypes. This tripartite approach stands to revolutionize the diagnostic process, offering a more comprehensive and nuanced understanding of the underlying genetic architecture that underpins prenatal anomalies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"37"},"PeriodicalIF":3.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788346","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":"Experiences of participants with undiagnosed diseases and hereditary cancers during the initial phase of the Hong Kong genome project: a mixed-methods study.","authors":"Annie Tw Chu, Samuel Yc Sze, Desiree Ms Tse, Cheryl Wy Lai, Carmen S Ng, Coco Ws Yu, Pui-Hong Chung, Fei-Chau Pang, Brian Hy Chung, Su-Vui Lo, Jianchao Quan","doi":"10.1186/s40246-025-00746-5","DOIUrl":"10.1186/s40246-025-00746-5","url":null,"abstract":"<p><strong>Background: </strong>The Hong Kong Genome Project (HKGP) is the first population-wide whole genome sequencing (WGS) programme in Hong Kong and aimed to integrate genomic medicine into the healthcare system. Implementing genetic counselling is essential to help participants understand the genetic basis of diseases and guide informed decision making. We assessed participant experiences during the initial HKGP pilot phase that enrolled patients with undiagnosed diseases and hereditary cancers.</p><p><strong>Methods: </strong>Participants were recruited from three partnering centres at public hospitals during June-September 2023. Participant surveys covered four domains: (1) overall satisfaction, (2) informed consent process, (3) genetic counselling, and (4) attitude towards HKGP. Associations with demographic and socioeconomic characteristics were assessed with multivariable logistic regression. Qualitative feedback was collected in focus group interviews.</p><p><strong>Results: </strong>Among 422 eligible participants, 341 completed the survey (80.8% response) and five focus group interviews were held (21 participants). We found 89.8% [95% CI: 86.1-92.7] were satisfied with their HKGP experience. Almost all felt that HKGP participation could benefit others (86.8% [95% CI: 82.7-90.0]) and advance genomic research in Hong Kong (88.9% [95% CI: 85.0-91.9]). The survey item with the lowest agreement among respondents was feeling that HKGP participation could improve their/child's medical treatment (73.5% [95% CI: 68.5-78.0]). Those with secondary and tertiary education were less likely to agree genetic counselling was helpful (Odds Ratio [OR]: 0.02 [95% CI: 0.001-0.41]; 0.02 [0.001-0.51]), or the appropriate length of time (OR: 0.12 [95% CI: 0.014-0.81]; 0.11 [0.01-0.91]). Focus group participants cited helping scientific advances and shortening the diagnostic odyssey of future patients as key reasons for participation. Participants hoped for a shorter reporting time of WGS results, additional medical follow-up, and allowing referral of relatives.</p><p><strong>Conclusions: </strong>Participants were overall highly satisfied with the HKGP and genetic counselling experience. Satisfaction levels were comparable to overseas genomic programmes and locally provided healthcare services. Participants' major concerns on WGS reporting time could be addressed by strengthening the informed consent process to ensure their expectations align with project implementation. Emphasizing the long-term value of genomic research and its potential for personalized treatments may increase participant engagement.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"36"},"PeriodicalIF":3.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788362","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 comparison of the expression patterns and diagnostic capability of the ncRNAs NEAT1 and miR-34a in non-obstructive azoospermia and severe oligospermia.","authors":"Aya Salman, Abdullah F Radwan, Olfat G Shaker, Adel A, Ghadir A Sayed","doi":"10.1186/s40246-025-00742-9","DOIUrl":"10.1186/s40246-025-00742-9","url":null,"abstract":"<p><p>Infertility is a major global health problem, affecting 8-12% of couples worldwide, with male causes contributing to approximately 50% of cases. Notably, around 15% of infertile men are azoospermic. Consequently, there is a critical necessity to find noninvasive biomarkers to help in diagnosing and assessing the susceptibility of patients with various infertility disorders. This study is designed to determine the roles of NEAT1 and miR-34a as diagnostic and susceptibility biomarkers for non-obstructive azoospermia and severe oligospermia. The interactions between these non-coding RNA (ncRNAs) were explored, along with their correlations to hormonal profiles and clinical parameters like sperm count and motility. The potential of serum NEAT1 and miR-34a as diagnostic biomarkers for these conditions was explored. The study included 100 participants: 40 non-obstructive azoospermia patients, 40 severe oligospermia patients, and 20 healthy controls. Quantitative real-time PCR and transcriptomics-based bioinformatics tools were employed to explore the co-expression networks and molecular interactions of NEAT1, miR-34a, SIRT1, and their associated hormonal and genetic pathways. Results indicated that NEAT1 was significantly downregulated in severe oligospermia patients, while its levels in non-obstructive azoospermia patients did not differ significantly from healthy controls. Furthermore, serum miR-34a expression was considerably upregulated in both patient groups compared to controls. This study highlights the promise of serum NEAT1 and miR-34a as diagnostic markers for non-obstructive azoospermia and severe oligospermia. These findings provide valuable insights into male infertility and indicate potential avenues for personalized treatment strategies.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"35"},"PeriodicalIF":3.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752363","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}