Human Genomics最新文献

{"title":"Dynamic profiling of Cell-free DNA fragmentation uncovers postprandial metabolic and immune alterations.","authors":"Ziting Zhu, Tao Chen, Manting Zhang, Xiaodi Shi, Pan Yu, Jianai Liu, Xiuzhi Duan, Zhihua Tao, Xuchu Wang","doi":"10.1186/s40246-025-00739-4","DOIUrl":"10.1186/s40246-025-00739-4","url":null,"abstract":"<p><strong>Background: </strong>Food intake affects body homeostasis and significantly changes circulating cell-free DNA (cfDNA). However, the source and elimination of postprandial cfDNA is difficult to trace, and it is unknown whether these changes can be revealed by cfDNA fragmentomics based on liquid biopsy.</p><p><strong>Methods: </strong>We performed shallow whole-genome sequencing of 30 plasma samples from 10 healthy individuals at fasting and postprandial (30-min and 2-h time points). We assessed the effect of postprandial states on cfDNA fragment size distribution and utilized deconvolutional analysis of end motifs to determine the potential roles of DNA nucleases in cfDNA fragmentation. We correlated the fragmentation index (defined as the ratio of short-to-long fragments) with gene expression to estimate the relative contribution of various cellular and tissue sources to cfDNA.</p><p><strong>Results: </strong>Compared to the fasting state, we observed a significant increase in short cfDNA fragments (70-150 bp) and a decrease in long fragments (151-250 bp) at the 30-minute postprandial state, followed by an inverse trend two hours later. Deconvolutional analysis of cfDNA end motifs showed that DNASE1L3 activity decreased at the 30-minute postprandial state, while DNASE1 and DFFB activities increased at the 2-hour postprandial state. We found that the expression of genes related to cellular metabolism and immune responses was upregulated at the postprandial state. Meanwhile, the contribution of cells and tissues involved in metabolic and immune progress to circulating plasma cfDNA was increased.</p><p><strong>Conclusions: </strong>The fragmentation of cfDNA is considerably influenced by postprandial states, highlighting the significance of taking postprandial effects into account when evaluating cfDNA as a biomarker. Furthermore, our study reveals the potential application of cfDNA fragmentation features in monitoring metabolic and immune status changes.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"27"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656726","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":"Correction: Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults.","authors":"Xiayin Zhang, Shan Wang, Shunming Liu, Zijing Du, Guanrong Wu, Yingying Liang, Yu Huang, Xianwen Shang, Yijun Hu, Zhuoting Zhu, Wei Sun, Xueli Zhang, Honghua Yu","doi":"10.1186/s40246-025-00737-6","DOIUrl":"10.1186/s40246-025-00737-6","url":null,"abstract":"","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"26"},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624474","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":"The CFTR K464N variant in fetuses potential increases premature birth risk in Chinese families.","authors":"Jingping Li, Lingyun Zhang, Fangfang Xi, Chuanping Lin, Qitao Zhan, Qing Zhou, Shi Zheng, Weikang Chen, Fan Jin","doi":"10.1186/s40246-025-00736-7","DOIUrl":"10.1186/s40246-025-00736-7","url":null,"abstract":"<p><strong>Background: </strong>Global fertility decline has led to increased use of assisted reproductive technology (ART), raising concerns about genetic risks to offspring. This study aimed to investigate cystic fibrosis transmembrane conductance regulator (CFTR) variants in Chinese families and assess their association with pregnancy complications and neonatal outcomes.</p><p><strong>Methods: </strong>This prospective cohort study included 446 Chinese families (148 natural conceptions, 298 ART conceptions) who underwent whole genome sequencing. We analyzed the frequency of pathogenic/likely pathogenic CFTR variants and their association with preterm birth (PTB), pregnancy complications, and neonatal outcomes.</p><p><strong>Results: </strong>Twelve pathogenic/likely pathogenic CFTR variants were identified, with K464N (c.1392G > T) being the most prevalent (2.9% of cohort). PTB incidence was significantly higher in pregnancies with fetal CFTR variants (43.1%, 22/51) compared to those without (17.5%, 69/395; p < 0.001). Fetuses carrying the CFTR K464N variant exhibited a 3.39-fold increased risk of PTB (95% confidence interval (CI): 1.39-8.23, p = 0.007) after adjusting for confounders. Neither fetal nor maternal CFTR variants were significantly associated with other neonatal outcomes, including neonatal weight, Apgar scores, respiratory distress, or hyperbilirubinemia (p > 0.050).</p><p><strong>Conclusion: </strong>These findings suggest a potential association between fetal CFTR K464N variant and increased risk of preterm birth in Chinese families, highlighting the importance of considering CFTR genotyping in prenatal care.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"25"},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614439","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":"Establishing a European wastewater pathogen monitoring network employing aviation samples: a proof of concept.","authors":"Robert Morfino, Bernd Manfred Gawlik, Simona Tavazzi, Angela Tessarolo, Ana Burgos Gutierrez, Nita K Madhav, Jasmine Grimsley, Amy Schierhorn, Andrew Franklin, Marta Vargha, Andrew Engeli, Mitchell Wolfe","doi":"10.1186/s40246-025-00725-w","DOIUrl":"10.1186/s40246-025-00725-w","url":null,"abstract":"<p><p>Pathogens know no borders, and the COVID-19 pandemic highlighted the urgent need for comparable, globally accessible pathogen data. This paper proposes a European wastewater pathogen monitoring network using aircraft and airport samples as a proof of concept for an effective cross-national surveillance system. The study emphasizes the importance of genomic data collection from strategic sites to produce high-value data for disease surveillance and epidemiological analysis. The authors suggest establishing \"Super Sites\" in key locations, particularly major transportation hubs like airports, to serve as focal points for wastewater-based pathogen surveillance. The European Commission has identified over 20 candidate Super Sites and supports their integration into a Global Wastewater Sentinel System. In October 2023, the European Commission's Joint Research Centre (JRC) and Ginkgo Bioworks conducted an ad hoc exercise, collecting and analyzing wastewater samples from airports and aircraft across Europe. This exercise demonstrated the feasibility of coordinated sampling, centralized processing, and data sharing across different countries. Samples were collected from eight airports over two weeks, employing various methods for different types of wastewater, including samples from terminals and aircraft. Across airports, 96% of wastewater samples tested positive for SARS-CoV-2, with similar viral loads between aircraft and airport sewage, and multiple lineages were identified, including the EG.5 variant, which is consistent with the publicly reported variant data. The results underscore the potential of routine aircraft wastewater monitoring as an early warning system for emerging pathogens. The study also highlights the need for standardized protocols and real-time reporting systems and the importance of addressing ethical considerations in handling passenger data. By creating a network of Super Sites, and integrating cross-national wastewater surveillance data with passenger flight data, the European Union aims to strengthen global public health responses to future pandemics. Establishing this surveillance network is a crucial step towards a pan-European surveillance system for pathogens, providing a non-intrusive complement to existing systems that rely on individual testing. This system will significantly improve early detection capabilities, leading to more rapid and robust responses and ultimately enhancing global health security.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"24"},"PeriodicalIF":3.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604724","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 the silent connection: unveiling the intricate relationship between gastroesophageal reflux disease and sleep apnea syndrome.","authors":"Junming Wang, Pengfei Wang, Jiang Lv, Ran Chen, Wei Yan, Daikun He","doi":"10.1186/s40246-025-00728-7","DOIUrl":"10.1186/s40246-025-00728-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Gastroesophageal reflux disease (GERD) and Sleep Apnea Syndrome (SAS) are two prevalent medical conditions that significantly affect health and quality of life. GERD involves stomach content reflux into the esophagus, while SAS causes recurrent upper airway obstruction during sleep. Despite recent studies hinting at a link, the precise relationship and causality between GERD and SAS remain unclear. Our research uses bidirectional Mendelian randomization to explore this intricate relationship. Additionally, given SAS's high prevalence in cardiovascular patients (40-80%, as highlighted by the American Heart Association), we also investigated its potential association with various cardiovascular diseases to gain new insights into prevention and treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study employed genetic data from large-scale genome-wide association studies (GWAS) on GERD (129,080 cases, 473,524 controls) and SAS (25,008 cases, 391,473 controls) for two-sample Mendelian randomization (MR) analysis to estimate the causal effects of GERD on the risk of SAS. All SNPs were selected using a strict clump window (r&lt;sup&gt;2&lt;/sup&gt; = 0.001 and kb = 10,000). We initially applied the inverse variance weighted (IVW) method and measured horizontal pleiotropy using MR-Egger, weighted median, and weighted mode methods. I&lt;sup&gt;2&lt;/sup&gt; index and Cochran Q statistics were used for sensitivity analysis. Funnel plot symmetry of IVW MR estimates versus 1/standard error (1/SEIV) was examined to exclude SNPs potentially causing heterogeneity. Additionally, to exclude reverse causality, bidirectional MR was employed to investigate whether genetic susceptibility to SAS causally influenced the risk of GERD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GERD was associated with an elevated risk of SAS, demonstrating an odds ratio (OR) of 1.750 (95% CI 1.590-1.930; P &lt; 0.001). Conversely, there was no compelling evidence to indicate a causal link between SAS and the risk of developing GERD, with an OR of 1.000 (95% CI 0.989-1.011; P = 0.964). In addition to the primary findings, our study also revealed significant risks associated with SAS for several cardiovascular conditions, including coronary heart disease, atrial fibrillation, coronary artery disease, heart failure, intracerebral hemorrhage, and ischemic stroke.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We discovered compelling evidence indicating an elevated risk of SAS in individuals with GERD, but no significant evidence supporting an increased risk of GERD in those with SAS. Future investigations into SAS risk should take into account the potential therapeutic targeting of GERD. PPI and histamine antagonists can effectively reduce reflux and airway secretions, preventing airway damage and collapse. Furthermore, it is necessary to investigate the underlying mechanisms by which GERD affects SAS. For example, the inflammatory stimulation caused by gastric acid and pepsin in refluxed fluid, as well as the","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"23"},"PeriodicalIF":3.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566934","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 landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort.","authors":"Yan Liu, Yang Sun, Qiuyi Huo, Linghao Song, Xinyue Wang, Xin Shen, Ye Zhao, Tianhui Chen, Yongxiang Jiang","doi":"10.1186/s40246-025-00729-6","DOIUrl":"10.1186/s40246-025-00729-6","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study is to elucidate the genetic landscape of microspherophakia (MSP) and describe the genotype-phenotype correlation of MSP. Additionally, the study seeks to enhance the understanding of the pathogenic mechanisms of MSP through the discovery of novel loci.</p><p><strong>Methods: </strong>Patients diagnosed with MSP at the Eye and ENT Hospital of Fudan University, Shanghai, were included in the study and all underwent panel-based next-generation sequencing and bioinformatics analysis. Comprehensive ophthalmologic evaluations were conducted for each participant.</p><p><strong>Results: </strong>Our analysis encompassed 118 eyes from 59 patients with MSP, revealing 13 gene variations linked to the condition. Notably, FBN1 mutations were identified in 31 patients (52.5%), highlighting its higher prevalence. Among the genetic variations discovered, 28 represented novel mutations. Statistical analysis unveiled significant associations between specific gene mutations and ocular biometric parameters: axial length (AL, p = 0.011), Z-score axial length (Z-AL, p < 0.001), white-to-white (WTW, p = 0.009), Z-score white-to-white (p = 0.012), mean keratometry (p < 0.001), astigmatism (AST, p = 0.021), anterior chamber depth (ACD, p = 0.003), lens thickness (LT, p = 0.012) and central endothelial cell count/mm2 (p = 0.005). Patients with FBN1 mutations had the longest AL, while those with CBS mutations showed significantly wilder WTW measurements. Patients with ADAMTS17 mutations presented with increased LT and decreased WTW, ADAMTSL4 mutations were linked to the greater Km and AST. Patients with LTBP mutations exhibited the largest WTW, and ASPH mutations was associated with the shortest AL but thick LT. Additionally, there was a relationship among gene mutations, diagnostic age and ocular biometric parameters.</p><p><strong>Conclusion: </strong>The study demonstrates that MSP is associated with a diverse range of genetic mutations, with FBN1 being the most common. Novel mutations were identified, and significant correlations were found between specific genetic variations and ocular biometric parameters. These results provide new insights into the genetic underpinnings of MSP and its clinical characteristics, advancing our understanding of the condition's pathogenic mechanisms.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"22"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537033","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":"Sengers syndrome caused by biallelic TIMM29 variants and RNAi silencing in Drosophila orthologue recapitulates the human phenotype.","authors":"Adel Shalata, Ann Saada, Mohammed Mahroum, Yarin Hadid, Chaya Furman, Zaher Eldin Shalata, Robert J Desnick, Avraham Lorber, Asaad Khoury, Adnan Higazi, Avraham Shaag, Varda Barash, Ronen Spiegel, Euvgeni Vlodavsky, Pierre Rustin, Shmuel Pietrokovski, Irena Manov, Dan Gieger, Galit Tal, Adi Salzberg, Hanna Mandel","doi":"10.1186/s40246-025-00723-y","DOIUrl":"10.1186/s40246-025-00723-y","url":null,"abstract":"<p><strong>Purpose: </strong>Sengers-syndrome (S.S) is a genetic disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. All reported cases were genetically caused by biallelic mutations in the AGK gene. We herein report a pathogenic variant in TIMM29 gene, encoding Tim29 protein, as a novel cause of S.S. Notably, AGK and Tim29 proteins are components of the TIM22 complex, which is responsible for importing carrier proteins into the inner mitochondrial membrane.</p><p><strong>Method: </strong>Clinical data of 17 consanguineous patients featuring S.S was obtained. Linkage analysis, and sequencing were used to map and identify the disease-causing gene. Tissues derived from the study participants and a Drosophila melanogaster model were used to evaluate the effects of TIMM29 variant on S.S.</p><p><strong>Results: </strong>The patients presented with a severe phenotype of S.S, markedly elevated serum creatine-phosphokinase, combined mitochondrial-respiratory-chain-complexes deficiency, reduced pyruvate-dehydrogenase complex activity, and reduced adenine nucleotide translocator 1 protein. Histopathological studies showed accumulation of abnormal mitochondria. Homozygosity mapping and gene sequencing revealed a biallelic variant in TIMM29 NM_138358.4:c.514T > C NP_612367.1:p.(Trp172Arg). The knockdown of the Drosophila TIMM29 orthologous gene (CG14270) recapitulated the phenotype and pathology observed in the studied cohort. We expand the clinical phenotype of S.S and provide substantial evidence supporting TIMM29 as the second causal gene of a severe type of S.S, designated as S.S- TIMM29.</p><p><strong>Conclusion: </strong>The present study uncovers several biochemical differences between the two S.S types, including the hyperCPKemia being almost unique for S.S-TIMM29 cohort, the different frequency of MMRCC and PDHc deficiencies among the two S.S types. We propose to designate the S.S associated with TIMM29 homozygous variant as S.S-TIMM29.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"21"},"PeriodicalIF":3.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531386","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 insights into cardiac conduction disorders from genome-wide association studies.","authors":"Bingxun Li, Hongxuan Xu, Lin Wu","doi":"10.1186/s40246-025-00732-x","DOIUrl":"10.1186/s40246-025-00732-x","url":null,"abstract":"<p><strong>Background: </strong>Substantial data support a heritable basis for cardiac conduction disorders (CCDs), but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood, therefore, we sought to identify genetic loci associated with CCDs.</p><p><strong>Methods: </strong>We performed meta-analyses of genome-wide association studies to identify genetic loci for atrioventricular block (AVB), left bundle branch block (LBBB), and right bundle branch block (RBBB) from public data from the UK Biobank and FinnGen consortium. We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and ECG-wide phenome-wide associations for each indexed SNP.</p><p><strong>Results: </strong>Analysis comprised over 700,000 individuals for each trait. We identified 10, 4 and 0 significant loci for AVB (PLEKHA3, TTN, FNDC3B, SENP2, SCN10A, RRH, PPARGC1A, PKD2L2, NKX2-5 and TBX20), LBBB (PPARGC1A, HAND1, TBX5, and ADAMTS5) and RBBB, respectively. Transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of SCN10A and AVB. Phenome-wide associations identified traits with both cardiovascular and non- cardiovascular traits with indexed SNPs.</p><p><strong>Conclusions: </strong>Our analysis highlight gene regions associated with channel function, cardiac development, sarcomere function and energy modulation as important potential effectors of CCDs susceptibility.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"20"},"PeriodicalIF":3.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531383","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 the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease.","authors":"Shuyan Zhang, Jiajun Wu, Leilei Wang, Cheng Zhang, Yinjian Zhang, Yibin Feng","doi":"10.1186/s40246-025-00730-z","DOIUrl":"10.1186/s40246-025-00730-z","url":null,"abstract":"<p><strong>Background: </strong>Dysfunctions within the liver system are intricately linked to the progression of diabetic retinopathy (DR) and non-alcoholic fatty liver disease (NAFLD). This study leverages systematic analysis to elucidate the complex cross-talk and communication pathways among diverse cell populations implicated in the pathogenesis of DR and NAFLD.</p><p><strong>Methods: </strong>Single-cell RNA sequencing data for proliferative diabetic retinopathy (PDR) and NAFLD were retrieved from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was conducted and followed by pseudo-time analysis to delineate dynamic changes in core cells and differentially expressed genes (DEGs). CellChat was employed to predict intercellular communication and signaling pathways. Additionally, gene set enrichment and variation analyses (GSEA and GSVA) were performed to uncover key functional enrichments.</p><p><strong>Results: </strong>Our comparative analysis of the two datasets focused on T cells, macrophages and endothelial cells, revealing SYNE2 as a notable DEG. Notably, common genes including PYHIN1, SLC38A1, ETS1 (T cells), PPFIBP1, LIFR, HSPG2 (endothelial cells), and MSR1 (macrophages), emerged among the top 50 DEGs across these cell types. The CD45 signaling pathway was pivotal for T cells and macrophages, exerting profound effects on other cells in both PDR and NAFLD. Moreover, GSEA and GSVA underscored their involvement in cellular communication, immune modulation, energy metabolism, mitotic processes.</p><p><strong>Conclusion: </strong>The comprehensive investigation of T cells, macrophages, endothelial cells, and the CD45 signaling pathway advances our understanding of the intricate biological processes underpinning DR and NAFLD. This research underscores the imperative of exploring immune-related cell interactions, shedding light on novel therapeutic avenues in these disease contexts.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"19"},"PeriodicalIF":3.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515383","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":"Causal effects of education, intelligence, and income on COVID-19: evidence from a Mendelian randomization study.","authors":"Yuqing Song, Ancha Baranova, Hongbao Cao, Weihua Yue, Fuquan Zhang","doi":"10.1186/s40246-025-00731-y","DOIUrl":"10.1186/s40246-025-00731-y","url":null,"abstract":"<p><strong>Background: </strong>The protective effects of higher educational attainment (EA) and intelligence on COVID-19 outcomes are not yet understood with regard to their dependency on income. The objective of our study was to examine the overall as well as independent effects of the three psychosocial factors on the susceptibility to and severity of COVID-19. To accomplish this, we utilized genetic correlation, Mendelian randomization (MR), and multivariable MR (MVMR) analyses to evaluate genetic associations between EA, intelligence, household income, and three specific COVID-19 outcomes: SARS-CoV-2 infection, hospitalized COVID-19, and critical COVID-19.</p><p><strong>Results: </strong>The genetic correlation analysis revealed that COVID-19 outcomes were negatively correlated with the three psychosocial factors (r_g: -0.19‒-0.36). The MR analysis indicated that genetic liability to EA, intelligence, and income exerted overall protective effects against SARS-CoV-2 infection (OR: 0.86‒0.92), hospitalized COVID-19 (OR: 0.70‒0.80), and critical COVID-19 (OR: 0.65‒0.85). MVMR analysis revealed that elevated levels of EA conferred independent protective effects against SARS-CoV-2 infection (OR: 0.85), hospitalization due to COVID-19 (OR: 0.79), and critical COVID-19 (OR: 0.63). Furthermore, intelligence exhibited a negative association with the risk of SARS-CoV-2 infection (OR: 0.91), whereas a higher income was linked to an elevated risk of SARS-CoV-2 infection (OR: 1.13).</p><p><strong>Conclusions: </strong>Our findings indicated that EA could significantly reduce the risk and severity of COVID-19, regardless of intelligence and income. However, the impact of intelligence or income on COVID-19 severity was not supported by our research.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":"19 1","pages":"18"},"PeriodicalIF":3.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500454","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}