Hereditas最新文献

{"title":"Exploring the bidirectional causality between neuroticism and frailty: a Mendelian randomization analysis.","authors":"Yuhang Xing, Rui Pu, Mengdie Fu, Zhikang Wang, Zhen Wang, Xiaopeng Shang, Guoli Yang, Zhiwei Jiang","doi":"10.1186/s41065-025-00370-2","DOIUrl":"10.1186/s41065-025-00370-2","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies have confirmed the relationship between personality trait neuroticism and physical health. However, the relationship between neuroticism and frailty remains unconfirmed. This study employed a bi-directional two-sample Mendelian randomization (MR) approach to investigate the causal relationship between neuroticism and frailty.</p><p><strong>Methods: </strong>The neuroticism genome-wide association study (GWAS) data from the UK Biobank contained twelve neuroticism-related traits with 489,212 participants. The genetic frailty index data were extracted from the UK Biobank and Swedish TwinGene, involving 175,226 individuals. Independent genetic variants associated with neuroticism and frailty were selected as instrumental variables. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and MR-PRESSO were mainly used for MR analysis.</p><p><strong>Results: </strong>The MR analysis showed a positive causal relationship between neuroticism and the risk of frailty (odds ratio (OR) = 1.627, 95% confidence interval (CI) = 1.538-1.722, P < 0.001). In the reverse direction, frailty had a causal effect on a higher risk of neuroticism (OR = 1.270, 95% CI = 1.173-1.375, P < 0.001). Steiger tests indicated that reverse causation did not bias the identified causal relationships.</p><p><strong>Conclusions: </strong>Our study provides genetic evidence suggesting a bi-directional causal relationship between frailty and neuroticism. In this bi-directional MR study, there were positive causal relationships between neuroticism-related phenotypes and frailty, and in the reverse direction, frailty was also positively correlated with neuroticism.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"8"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-dependent DLG2 inhibits the malignant progression of cervical cancer by inactivating the Hippo/YAP signaling.","authors":"Mei Pu, Xia Xiao, Shasha Lv, Daqing Ran, Qian Huang, Mingming Zhou, Qirong Lei, Lingshuang Kong, Qing Zhang","doi":"10.1186/s41065-025-00365-z","DOIUrl":"10.1186/s41065-025-00365-z","url":null,"abstract":"<p><strong>Background: </strong>Discs large homolog 2 (DLG2) has been implicated in cancer development, yet its role in cervical cancer remains unclear. This study aims to explore the regulatory mechanism of DLG2 in cervical cancer and its clinical implications.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction and western blotting assays were employed to detect RNA and protein expression, respectively. Colony formation assay, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, and transwell assays were conducted for cell functional analysis. A xenograft mouse model assay was performed to analyze tumor tumorigenesis in vivo. m6A RNA immunoprecipitation assay was used to analyze the association of METTL3 and DLG2.</p><p><strong>Results: </strong>DLG2 was underexpressed in cervical cancer tissues and cells. Elevating DLG2 levels significantly suppressed cervical cancer cell proliferation, migration, and invasion, while promoting apoptosis. Additionally, DLG2 overexpression led to the deactivation of the Hippo/YAP signaling pathway. In vivo, DLG2 overexpression was shown to reduce tumor formation. We also discovered that METTL3 destabilized DLG2 mRNA through an m6A-dependent mechanism. Moreover, lowering DLG2 expression mitigated the effects of METTL3 silencing on cervical cancer cell malignancy.</p><p><strong>Conclusion: </strong>DLG2 acted as a tumor suppressor in cervical cancer by inhibiting the Hippo/YAP signaling pathway. The METTL3-dependent regulation of DLG2 mRNA stability could be a critical factor in cervical cancer progression.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"9"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal association among smoking, bitter beverage consumption, and risk of osteoporosis: a two-sample mendelian randomization-based study.","authors":"Yanqian Wu, Jianqian Chao, Min Bao, Na Zhang, Leixia Wang","doi":"10.1186/s41065-025-00371-1","DOIUrl":"10.1186/s41065-025-00371-1","url":null,"abstract":"<p><strong>Objectives: </strong>Two-sample MR methods were employed to analyze the impact of smoking and bitter beverage consumption on the risk of osteoporosis and osteoporosis with pathological fractures, in order to assess the causal association.</p><p><strong>Methods: </strong>Publicly available genome-wide association study summary data were analyzed using MR methods. The exposures investigated were smoking (smoking per day, smoking initiation, and lifetime smoking index) and bitter beverages (coffee, tea, bitter alcoholic beverages, bitter non-alcoholic beverages, and total bitter beverages). The outcomes examined were the risk of osteoporosis and osteoporosis with pathological fractures. The inverse-variance weighted (IVW) method was used as the main statistical model. The stability and reliability of the results were verified by the Cochran's Q test, the Egger-intercept test, and the leave-one-out analysis.</p><p><strong>Results: </strong>Smoking per day was causally associated with the risk of osteoporosis OR = 1.417, 95% CI = 1.119-1.794, P = 0.003), and lifetime smoking index had a possible genetic causal association with the risk of osteoporosis with pathological fractures (OR = 4.187, 95% CI = 1.909-9.184, P < 0.001). No genetic causal association was found between smoking initiation or lifetime smoking index and the risk of osteoporosis (P > 0.05). No genetic causal association was identified between smoking per day or smoking initiation and the risk of osteoporosis with pathological fractures (P > 0.05). Total and bitter non-alcoholic beverage consumption showed a potential effect on the risk of osteoporosis (OR = 3.687, 95% CI = 1.535-8.858, P = 0.003 and OR = 3.040, 95% CI = 1.466-6.304, P = 0.002, respectively).</p><p><strong>Conclusions: </strong>This study found smoking raises the risk of osteoporosis and osteoporosis with pathological fractures based on genetics. Certain bitter beverages are linked to an increased osteoporosis risk.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"7"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the potential ability of DExD/H-box helicase 60 (DDX60) on the proliferation, diagnostic and prognostic biomarker in pancreatic cancer: a research based on silico, RNA-seq and molecular biology experiment.","authors":"Dongdong Zhang, Enze Zhang, Ying Cai, Yixin Sun, Peiji Zeng, Xiaohua Jiang, Yifan Lian","doi":"10.1186/s41065-024-00361-9","DOIUrl":"10.1186/s41065-024-00361-9","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is one of the most malignant abdominal tumors. DDX60 has been shown to be associated with a variety of tumor biological processes. However, DDX60 in pancreatic cancer has not been reported. Our study confirmed that DDX60 can serve as a novel biomarker for diagnosis and treatment of pancreatic cancer.</p><p><strong>Materials and methods: </strong>We downloaded pancreatic cancer datasets from GEO and TCGA databases, respectively. To investigate the relationship between DDX60 expression and prognosis in pancreatic cancer. GSEA analysis was performed on DDX60. We performed RNA-seq to further explore the downstream biological targets of DDX60 and the signaling pathways that may be involved in pancreatic cancer. Finally, we tested it through molecular biology experiments. First, we constructed the plasmid and tested the plasmid effect by WB. Then MTT assay was performed to explore the effect of DDX60 knockout on the proliferation of pancreatic cancer cells. LDH assay was performed to explore the effect of DDX60 on the release of lactate dehydrogenase from tumor cells. The effect of DDX60 on cell proliferation was further explored by clonal formation experiment. Continue to explore clinical therapeutic drugs sensitive to DDX60 targets.</p><p><strong>Results: </strong>By analyzing the GSE71729, GSE183795, GSE16515, GSE28735 and GSE62452 data sets, we found that DDX60 was highly expressed in pancreatic cancer. And is associated with poorer outcomes for pancreatic patients. The mRNA expression level of DDX60 was correlated with lymph node metastasis and grade in clinical pancreatic patients. Through the results of RNA-seq analysis, GO and KEGG analysis showed that DDX60 may be associated with cell cycle in pancreatic cancer. Through molecular biology experiments (MTT, LDH, and clonal formation experiment), we found that When DDX60 is knocked down in pancreatic cancer cells, the proliferation ability of tumor cells is significantly decreased. Several drugs targeting about DDX60 have been found, such as JW-7-52-1, this could provide direction for drug therapy against the DDX60 target.</p><p><strong>Conclusion: </strong>In summary, DDX60 can be used as a novel biomarker related to the diagnosis and treatment of pancreatic cancer, participate in tumor proliferation, and is associated with poor prognosis in patients.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"6"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key wound healing genes as diagnostic biomarkers and therapeutic targets in uterine corpus endometrial carcinoma: an integrated in silico and in vitro study.","authors":"Fuchuan Jiang, Sajjad Ahmad, Sadia Kanwal, Yasir Hameed, Qian Tang","doi":"10.1186/s41065-025-00369-9","DOIUrl":"10.1186/s41065-025-00369-9","url":null,"abstract":"<p><strong>Background: </strong>Uterine Corpus Endometrial Carcinoma (UCEC) is a prevalent gynecologic malignancy with complex molecular underpinnings. This study identifies key woundhealing genes involved in UCEC and elucidates their roles through a comprehensive analysis.</p><p><strong>Methods: </strong>In silico and in vitro experiments.</p><p><strong>Results: </strong>Seventy wound healing-associated genes were extracted from the Gene Ontology (GO) database, and a protein-protein interaction (PPI) network was constructed using the STRING database. CytoHubba analysis in Cytoscape identified six pivotal hub genes: CD44, FGF2, FGF10, KDM6A, FN1, and MMP2. These genes exhibited significantly lower expression in UCEC cell lines compared to normal controls, as confirmed by RT-qPCR. Receiver Operating Characteristic (ROC) analysis demonstrated their potential as diagnostic biomarkers, with Area Under the Curve (AUC) values ranging from 0.94 to 1.00. Validation using TCGA datasets revealed consistent downregulation of these genes in UCEC samples, corroborated by immunohistochemical staining. Promoter methylation analysis showed significantly higher methylation levels in UCEC, correlating with decreased mRNA expression and poor survival outcomes. Genetic alteration analysis indicated frequent mutations in FN1 and KDM6A, although these did not significantly affect survival. Functional analysis using the CancerSEA database highlighted the involvement of these genes in critical cancer-related processes, including angiogenesis, apoptosis, and metastasis. Immune correlation studies revealed significant associations with immune inhibitor genes and distinct expression patterns across immune subtypes. Overexpression studies in UCEC cell lines demonstrated that CD44 and MMP2 reduce proliferative ability while enhancing migration and wound healing.</p><p><strong>Conclusion: </strong>Collectively, these findings underscore the crucial roles of CD44, FGF2, FGF10, KDM6A, FN1, and MMP2 in UCEC pathogenesis, highlighting their potential as biomarkers and therapeutic targets in this malignancy.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"5"},"PeriodicalIF":2.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mir-615-5p inhibits cervical cancer progression by targeting TMIGD2.","authors":"Yan Zhao, Haitao Chen, Wenhui Zhang, Wei Shang, Jinwei Cao, Huijuan Zhao, Zhixiang Zou","doi":"10.1186/s41065-024-00363-7","DOIUrl":"10.1186/s41065-024-00363-7","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is a prevalent gynecological malignancy, contributing to a substantial number of fatalities among women. MicroRNAs (miRNAs) have emerged as promising biomarkers with significant potential for the early detection and prognosis of CC.</p><p><strong>Objective: </strong>This study aimed to explore the clinical significance and biological role of miR-615-5p in CC, with the goal of identifying novel biomarkers for this disease.</p><p><strong>Materials and methods: </strong>The levels of miR-615-5p and TMIGD2 mRNA in tissue samples and cells were quantified through quantitative reverse transcription real-time PCR, followed by statistical analyses to investigate the correlation between miR-615-5p and clinical data. The effects of miR-615-5p on the proliferation and metastasis of CC cells were evaluated using the Cell Counting Kit-8 and Transwell assays. The potential mechanism of miR-615-5p was elucidated by bioinformatics analyses and Dual-luciferase reporter assay. Western blotting was employed to measure the protein levels of TMIGD2.</p><p><strong>Results: </strong>In CC, the downregulation of miR-615-5p was related to poor prognosis and emerged as an independent prognostic factor. The levels of miR-615-5p were reduced in CC cells. miR-615-5p overexpression restrained the proliferation and metastasis of CC cells. Furthermore, TMIGD2 was identified as a target gene regulated by miR-615-5p, and its expression was notably elevated in CC. The influence of miR-615-5p on the biological behaviors of CC cells was mediated through the modulation of TMIGD2.</p><p><strong>Conclusions: </strong>Downregulation of miR-615-5p was a prognostic indicator of poor prognosis in CC. miR-615-5p exerted its tumor-suppressive effects by inhibiting cell growth and metastasis through the regulation of TMIGD2.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"4"},"PeriodicalIF":2.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Mendelian randomization analysis to explore causal associations of aspirin use with bone mineral density and risk of fracture.","authors":"Qi-Pei Liu","doi":"10.1186/s41065-024-00359-3","DOIUrl":"https://doi.org/10.1186/s41065-024-00359-3","url":null,"abstract":"<p><strong>Objective: </strong>Previous observational studies on the association between aspirin use, bone mineral density (BMD), and fracture risk have yielded controversial results. This study explored the causal relationship between aspirin use, BMD, and fracture risk using Mendelian randomization (MR).</p><p><strong>Methods: </strong>Summary data for aspirin use and BMD of five different body parts (femoral neck, lumbar spine, forearm, heel, and ultra distal forearm) and fractures were obtained from the integrative epidemiology unit open genome-wide association studies database for bidirectional MR analysis. An appropriate model was chosen based on Cochran's Q test, with inverse variance-weighted as the primary method for MR analysis, supplemented by the weighted-median and MR-Egger methods. MR-Egger and MR-PRESSO were used to test for horizontal pleiotropy and exclude significant outliers that could bias the results. Various sensitivity analyses, including leave-one-out analysis, were conducted to ensure the robustness of the findings.</p><p><strong>Results: </strong>Aspirin use significantly increased lumbar spine BMD (odds ratio [OR] = 4.660; 95% confidence interval [CI]: 1.365-15.906; P = 0.014). No significant causal association was found between aspirin use and fracture risk (beta = 59.951; 95% CI: -265.189-385.091; P = 0.718). No significant reverse causality was observed.</p><p><strong>Conclusion: </strong>This study indicates that aspirin use does not significantly affect fracture risk but has a significant protective effect on lumbar spine BMD, revealing a potential benefit of aspirin against osteoporosis.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"3"},"PeriodicalIF":2.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's disease and antibody-mediated immune responses to infectious diseases agents: a mendelian randomization study.","authors":"Jiayuan Zhang, Mingming Wang, Dong Wang, Linwen Deng, Yao Peng","doi":"10.1186/s41065-024-00358-4","DOIUrl":"10.1186/s41065-024-00358-4","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, with antibody-mediated immune responses to infectious diseases agents potentially playing a decisive role in its pathophysiological process. However, the causal relationship between antibodies and AD remains unclear.</p><p><strong>Methods: </strong>A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal link between antibody-mediated immune responses to infectious diseases agents and the risk of AD. Genetic variations associated with these antibodies obtained from UK Biobank, and data on AD were obtained from the Finnish databases, utilizing its extensive repository of genome-wide association studies (GWAS) for a comprehensive analysis. The MR analysis employed the inverse variance-weighted, MR-Egger, and weighted median methods. Sensitivity analysis was also performed using MR-Egger regression, MR-pleiotropy residual sum, and outlier tests.</p><p><strong>Results: </strong>Two causal associations were identified between antibody-mediated immune responses to infectious diseases agents and AD. Varicella zoster virus glycoproteins E and I antibody suggest a protective association with AD. Conversely, higher levels of Epstein-Barr virus EBNA-1 antibody appear to be associated with an increased risk of AD.</p><p><strong>Conclusion: </strong>Our MR analysis has revealed a causal relationship between antibody-mediated immune responses to specific infectious disease agents and AD. These findings provide valuable insights into the pathophysiological mechanisms underlying AD.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"2"},"PeriodicalIF":2.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory insights of monoterpene glycosides in endometriosis: immune infiltration and target pathways analysis.","authors":"Jin Zhan, Jiajie Wu","doi":"10.1186/s41065-024-00354-8","DOIUrl":"https://doi.org/10.1186/s41065-024-00354-8","url":null,"abstract":"<p><p>Endometriosis is a complex gynecological condition characterized by abnormal immune responses. This study aims to explore the immunomodulatory effects of monoterpene glycosides from Paeonia lactiflora on endometriosis. Using the ssGSEA algorithm, we assessed immune cell infiltration levels between normal and endometriosis groups. Key targets were identified through differential expression analysis of the GSE51981 dataset. Potential immunomodulatory targets of Paeonia lactiflora compounds were identified through Venn diagram analysis, followed by enrichment and machine learning analyses. A nomogram was developed for predicting endometriosis, while molecular docking explored compound-target interactions. Significant differences in immune cell infiltration were observed, with increased CD8 T cells, cytotoxic cells, and others in endometriosis. Differential expression analysis identified 43 potential targets. Enrichment analysis highlighted pathways involved in immune and inflammatory responses. Machine learning identified SSTR5, CASP3, FABP2, and SYK as critical targets, contributing to a nomogram that demonstrated good predictive performance for endometriosis risk. Molecular docking revealed strong interactions between Paeoniflorigenone and CASP3. Our findings suggest that monoterpene glycosides have therapeutic effects on endometriosis by modulating key immune-related targets and pathways, providing a basis for further investigation into Paeonia lactiflora's potential as a treatment for this condition.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"1"},"PeriodicalIF":2.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between bone mineral density and scoliosis: a two-sample mendelian randomization study in european populations.","authors":"Fangjun Yang, Jiantao Wen","doi":"10.1186/s41065-024-00352-w","DOIUrl":"10.1186/s41065-024-00352-w","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that bone mineral density (BMD) has a certain impact on scoliosis. However, up to now, there is no clear evidence that there is a causal association between the two. The aim of this study is to investigate whether there is a causal association between BMD at different body positions and scoliosis by two-sample Mendelian randomization (MR).</p><p><strong>Methods: </strong>Genetic variants (SNPS) strongly associated with BMD (total body BMD (TB-BMD), lumbar spine BMD (LS-BMD), femoral neck BMD (FN-BMD), heel BMD (HE-BMD), and forearm BMD (FA-BMD)) were extracted from GEFOS and genome-wide association analysis (GWAS) databases SNPs) were used as instrumental variables (IVs). Scoliosis was also selected from the Finnish database as the outcome. Inverse variance weighting (IVW) method was used as the main analysis method, and multiple sensitivity analysis was performed by combining weighted median, MR-Egger, MR Multi-effect residuals and outliers.</p><p><strong>Results: </strong>IVW results showed that TB-BMD (OR = 0.83, 95%CI: 0.66-1.55 P = 0.13), LS-BMD (OR = 0.72, 95%CI: 0.52-0.99, P = 0.04), FN-BMD (OR = 0.74, 95%CI: 0.50-1.09, P = 0.13), FA-BMD (OR = 0.95,95%CI: 0.70-1.28, P = 0.75), HE-BMD (OR = 0.91, 95%CI: 0.77-1.08, P = 0.29). Sensitivity analyses showed no evidence of pleiotropy or heterogeneity (p > 0.05) (MR-PRESSO and Cochrane). The results were further validated by leave-one-out test and MR-Egger intercept, which confirmed the robustness of the study results.</p><p><strong>Conclusion: </strong>In conclusion, the present study demonstrates that the causal role of genetic prediction of scoliosis increases with decreasing lumbar BMD. There was no evidence that BMD at the remaining sites has a significant causal effect on scoliosis. Our results suggest that the lumbar spine BMD should be routinely measured in the population at high risk of scoliosis. If osteoporosis occurs, appropriate treatment should be given to reduce the incidence of scoliosis.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"161 1","pages":"57"},"PeriodicalIF":2.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}