medRxiv - Epidemiology最新文献

{"title":"Genomic epidemiology reveals 2022 mpox epidemic in New York City governed by heavy-tailed sexual contact networks","authors":"Jonathan E Pekar, Yu Wang, Jade C Wang, Yucai Shao, Faten Taki, Lisa A Forgione, Helly Amin, Tyler Cabby, Kimberly Johnson, Lucia V Torian, Sarah L Braunstein, Preeti Pathela, Enoma Omoregie, Scott Hughes, Marc A Suchard, Tetyana I Vasylyeva, Philippe Lemey, Joel O Wertheim","doi":"10.1101/2024.07.30.24311083","DOIUrl":"https://doi.org/10.1101/2024.07.30.24311083","url":null,"abstract":"The global mpox epidemic in 2022 was likely caused by transmission of mpox virus (MPXV) through sexual contact networks, with New York City (NYC) experiencing the first and largest outbreak in the United States. By performing a phylogeographic and epidemiological analysis of MPXV, we identify at least 200 introductions of MPXV into NYC and 84 leading to onward transmission. Through a comparative analysis with human immunodeficiency virus (HIV) in NYC, we find that both MPXV and HIV genomic cluster sizes are best fit by scale-free distributions and that people in MPXV clusters are more likely to have previously received an HIV diagnosis (odds ratio=1.58; p=0.012) and be a member of a recently growing HIV transmission cluster, indicating overlapping sexual contact networks. We then model the transmission of MPXV through sexual contact networks and show that highly connected individuals would be disproportionately infected at the start of an epidemic, thereby likely resulting in the exhaustion of the most densely connected parts of the sexual network. This dynamic explains the rapid expansion and decline of the NYC outbreak, as well as the estimated cumulative incidence of less than 2% within high-risk populations. By synthesizing the genomic epidemiology of MPXV and HIV with epidemic modeling, we demonstrate that MPXV transmission dynamics can be understood by general principles of sexually transmitted pathogens.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleiotropic and sex-specific genetic architecture of circulating metabolic markers","authors":"Dennis van der Meer, Zillur Rahman, Aigar Ottas, Pravesh Parekh, Gleda Kutrolli, Sara Stinson, Maria Koromina, Jaroslav Rokicki, Ida Sonderby, Nadine Parker, Markos Tesfaye, Guy Hindley, Linn Rodevand, Elise Koch, Nils Steen, Jens Berg, Kevin O'Connell, Olav Smeland, Oleksandr Frei, Anders Dale, Srdjan Djurovic, Kelli Lehto, Maris Alver, Lili Milani, Alexey Shadrin, Ole Andreassen","doi":"10.1101/2024.07.30.24311254","DOIUrl":"https://doi.org/10.1101/2024.07.30.24311254","url":null,"abstract":"Background: Metabolites in plasma form biosignatures of a range of common complex human diseases. Mapping the genetic architecture and discovering variants with pleiotropic effects across metabolites can reveal underlying mechanisms and potential targets for personalized interventions.\u0000Methods: We performed univariate and multivariate genome-wide association studies (GWAS) on the Nightingale panel of 249 circulating plasma metabolic markers, across 207,836 White British UK Biobank participants (mean age 57.4 years, 53.7% female), with replication conducted across 27,509 UK Biobank participants with different ancestries, and 92,661 Estonian Biobank participants (mean age 50.9 years, 65.7% female). We investigated rare variation through whole exome sequencing gene burden tests, quantified genetic architectures through Gaussian mixture modelling, analysed the causal role of body mass index (BMI) through Mendelian randomization, and performed genome-wide interaction analyses with sex.\u0000Results: We discovered 14,837 loci (497 unique), with shared and distinct effects on cardiometabolic traits, with high replication rates across populations. The loci explained over 70% of genetic variance for fatty acids. Findings from common and rare variant gene tests converged on lipid homeostasis pathways. There was strong evidence for causal effects of BMI on cholesterol and amino acid levels. We discovered 31 loci interacting with sex, which mapped to genes involved in cholesterol processing, and to cardiometabolic conditions with sex differences in prevalence.\u0000Discussion: The findings offer new insights into the genetic architecture of circulating metabolites, revealing novel loci and plausible sex-specific molecular mechanisms of lipid metabolism. This improved understanding of the molecular biology of metabolism lays a foundation for personalized prevention and treatment strategies.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"170 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the transformative potential of data science in improving maternal, newborn and child health in Africa: A scoping review protocol","authors":"Akuze Joseph Waiswa, Bancy Ngatia, Samson Yahannes Amare, Phillip Wanduru, Grieven P Otieno, Rornald Muhumuza Kananura, Fati Kirakoya-Samadoulougou, Agbessi Amouzou, Abiy Seifu Estifanos, Eric O Ohuma","doi":"10.1101/2024.07.31.24311286","DOIUrl":"https://doi.org/10.1101/2024.07.31.24311286","url":null,"abstract":"ABSTRACT Introduction: Application of data science in Maternal, Newborn, and Child Health (MNCH) across Africa is variable with limited documentation. Despite efforts to reduce preventable MNCH morbidity and mortality, progress remains slow. Accurate data is crucial for holding countries accountable, tracking progress towards realisation of SDG3 targets on MNCH, and guiding interventions. Data science can improve data availability, quality, healthcare provision, and decision-making for MNCH programs. We aim to map and synthesise use cases of data science in MNCH across Africa.\u0000Methods and Analysis: We will develop a conceptual framework encompassing seven domains: Infrastructure and Systemic Challenges, Data Acquisition, Data Quality, Governance, Regulatory Dynamics and Policy, Technological Innovations and Digital Health, Capacity Development, Human Capital, Collaborative and Strategic Frameworks, data analysis, visualization, dissemination and Recommendations for Implementation and Scaling. A scoping review methodology will be used including literature searches in seven databases, grey literature sources and data extraction from the Digital Health Initiatives database. Three reviewers will screen articles and extract data. We will synthesise and present data narratively, and use tables, figures, and maps. Our structured search strategy across academic databases and grey literature sources will find relevant studies on data science in MNCH in Africa. Ethics and dissemination: This scoping review require no formal ethics, because no primary data will be collected. Findings will showcase gaps, opportunities, advances, innovations, implementation, areas needing additional research and propose next steps for integration of data science in MNCH programs in Africa. The findings' implications will be examined in relation to possible methods for enhancing data science in MNCH settings, such as community, and clinical settings, monitoring and evaluation. This study will illuminate data science applications in addressing MNCH issues and provide a holistic view of areas where gaps exist and where there are opportunities to leverage and tap into what already exists. The work will be relevant for stakeholders, policymakers, and researchers in the MNCH field to inform planning. Findings will be disseminated through peer-reviewed journals, conferences, policy briefs, blogs, and social media platforms in Africa.\u0000Keywords: Data Science, Maternal Health, Newborn and Perinatal Health, Child Health, Africa","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toscana Virus Infection Clinical Characterization","authors":"Remi N Charrel, Carole Eldin, Nazli Ayhan","doi":"10.1101/2024.07.31.24310805","DOIUrl":"https://doi.org/10.1101/2024.07.31.24310805","url":null,"abstract":"Background: Toscana virus (TOSV) is a sandfly-borne phlebovirus causing central nervous system (CNS) infection in Mediterranean countries, during summer season. However, clinical aspects of the disease caused by this virus are poorly known by clinicians, so that its prevalence is probably underestimated due to a lack of diagnosis.\u0000Study design: We gathered data from all available case series and retrospective studies identifying TOSV as the causative viral agent. The informations of age, sex, clinical characteristics, laboratory findings, imaging results and clinical outcomes of TOSV infection were recorded and analyzed. Results: In our review a total of 95 articles including TOSV infections resulting in a total of 1,381 cases were analyzed. Our findings indicate, TOSV affects individuals across various age groups, with a median age of 44.45 years. A notable disparity in infection rates between genders, with men being significantly more likely to present symptoms due to TOSV than women, with a sex ratio of 2.0 (p<0.001). The clinical presentation of TOSV infection encompasses a range of symptoms, including fever, headache, retro-orbital pain, neurological and muscular manifestations with less common reports of cutaneous and gastrointestinal symptoms. To date, six fatalities have been attributed to TOSV infections, with a median age of 76 years. Diagnostic evaluation of TOSV infections often involves the analysis of cerebrospinal fluid, where findings may include an elevated white blood cell count.\u0000Conclusions: These findings underscore the diverse clinical manifestations of TOSV infections and highlight the importance of considering this pathogen in the differential diagnosis of patients presenting with acute febrile illness, especially in endemic regions. TOSV represents an emerging infectious threat that warrants inclusion in the diagnostic protocols for patients presenting with CNS, particularly within the Mediterranean basin or for those with recent travel history to endemic regions during warmer months when sandflies are actively circulating.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A One Health Investigation into H5N1 Avian Influenza Virus Epizootics on Two Dairy Farms","authors":"Ismaila Shittu, Diego Silva, Judith U. Oguzie, Lyudmyla V. Marushchak, Gene G. Olinger, John A. Lednicky, Claudia M. Trujillo-Vargas, Nicholas E. Schneider, Haiping Hao, Gregory C. Gray","doi":"10.1101/2024.07.27.24310982","DOIUrl":"https://doi.org/10.1101/2024.07.27.24310982","url":null,"abstract":"Background: In early April 2024 we studied two Texas dairy farms which had suffered incursions of H5N1 highly pathogenic avian influenza virus (HPAIV) the previous month. Methods: We employed molecular assays, cell and egg culture, Sanger and next generation sequencing to isolate and characterize viruses from multiple farm specimens (cow nasal swab, milk specimens, fecal slurry, and a dead bird). Results: We detected H5N1 HPAIV in 64% (9/14) of milk specimens, 2.6% (1/39) of cattle nasal swab specimens, and none of 17 cattle worker nasopharyngeal swab specimens. We cultured and characterized virus from eight H5N1-positive specimens. Sanger and next-generation sequencing revealed the viruses were closely related into other recent Texas epizootic H5N1 strains of clade 2.3.4.4b. Our isolates had multiple mutations associated with increased spillover potential. Surprisingly, we detected SARS-CoV-2 in a nasal swab from a sick cow. Additionally, 14.3% (2/14) of the farm workers who donated sera were recently symptomatic and had elevated neutralizing antibodies against a related H5N1 strain. Conclusions: While our sampling was limited, these data offer additional insight into the large H5N1 HPAIV epizootic which thus far has impacted at least 96 cattle farms in twelve US states. Due to fears that research might damage dairy businesses, studies like this one have been few. We need to find ways to work with dairy farms in collecting more comprehensive epidemiological data that are necessary for the design of future interventions against H5N1 HPAIV on cattle farms.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multivariable Mendelian randomization to disentangle the alcohol 1 harm paradox.","authors":"Gemma Sawyer, Hannah Sallis, Marcus Munafo, Liam Mahedy, Jasmine N Khouja","doi":"10.1101/2024.07.30.24311209","DOIUrl":"https://doi.org/10.1101/2024.07.30.24311209","url":null,"abstract":"The alcohol harm paradox, whereby low socioeconomic position (SEP) groups experience greater alcohol-related harms despite reporting lower alcohol consumption, is yet to be fully understood through observational studies because key drivers are correlated and share similar confounding structures. Multivariable Mendelian randomization (MVMR) were conducted to estimate the direct causal effect of number of drinks per week (DPW) and years of schooling (YOS) on multiple health outcomes. Previously published genome-wide association summary (GWAS) statistics for DPW and YOS were utilised, and summary statistics were generated from individual-level data from UK Biobank (N = 462,818) for all health outcomes. Inverse variance weighted analyses demonstrated evidence for direct effects of DPW and YOS on liver diseases, mental and behavioural disorders due to alcohol, and stroke, indicating that increasing alcohol consumption increased the likelihood of outcomes whereas increasing years of education decreased their likelihood. There was also evidence for a direct effect of DPW on depression, anxiety, influenza/pneumonia, and heart disease. In contrast, there was evidence of a total, but not direct, effect of DPW on depression, influenza/pneumonia, epilepsy, and injuries when accounting for YOS. Although caution is required when interpreting these results due to weak instruments for alcohol, these results provide some evidence that the alcohol harm paradox is partially due to the protective effect of additional years of education, resulting in a reduced likelihood of higher SEP groups developing many alcohol-related outcomes. Replication with strong instruments would be necessary to draw causal inferences.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Machine Learning-enabled SIR Model for Adaptive and Dynamic Forecasting of COVID-19","authors":"Peter Mortensen, Katharina Lauer, Stefan Petrus Rautenbach, Marco Gallotta, Natasha Sharapova, Ioannis Takkides, Michael Wright, Matthew Linley","doi":"10.1101/2024.07.30.24311170","DOIUrl":"https://doi.org/10.1101/2024.07.30.24311170","url":null,"abstract":"The COVID-19 pandemic has posed significant challenges to public health systems worldwide, necessitating accurate and adaptable forecasting models to manage and mitigate its impacts. This study presents a novel forecasting framework based on a Machine Learning-enabled Susceptible-Infected-Recovered (ML-SIR) model with time-varying parameters to predict COVID-19 dynamics across multiple geographies. The model incorporates emergent patterns from reported time-series data to estimate new hospitalisations, hospitalised patients, and new deaths. Our framework adapts to the evolving nature of the pandemic by dynamically adjusting the infection rate parameter over time and using a Fourier series to capture oscillating patterns in the data. This approach improves upon traditional SIR and forecasting models, which often fail to account for the complex and shifting dynamics of COVID-19 due to new variants, changing public health interventions, and varying levels of immunity. Validation of the model was conducted using historical data from the United States, Italy, the United Kingdom, Canada, and Japan. The model's performance was evaluated based on the Mean Absolute Percentage Error (MAPE) and Absolute Percentage Error of Cumulative values (CAPE) for three-month forecast horizons. Results indicated that the model achieved an average MAPE of 32.5% for new hospitalisations, 34.4% for patients, and 34.8% for new deaths, for three-month forecasts. Notably, the model demonstrated superior accuracy compared to existing forecasting models with like-for-like disease metrics, countries and forecast horizons. The proposed ML-SIR model offers a robust and adaptable tool for forecasting COVID-19 dynamics, capable of adjusting to new time-series data and varying geographical contexts. This adaptability makes it suitable for localised hospital capacity planning, scenario modelling, and for application to other respiratory infectious diseases with similar transmission dynamics, such as influenza and RSV. By providing reliable forecasts, the model supports informed public health decision-making and resource allocation, enhancing preparedness and response efforts.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do smoking and alcohol behaviours influence risk of type 2 diabetes? A Mendelian randomisation study.","authors":"Zoe E Reed, Hannah M Sallis, Rebecca C Richmond, Angela S Attwood, Deborah A Lawlor, Marcus R Munafo","doi":"10.1101/2024.07.26.24311054","DOIUrl":"https://doi.org/10.1101/2024.07.26.24311054","url":null,"abstract":"Background: Previous studies suggest that smoking and higher alcohol consumption are both associated with greater risk of type 2 diabetes (T2D). However, studies examining whether these associations reflect causal relationships are limited and do not consider continuous glycaemic traits. The aim of the study was to determine whether there are causal effects of smoking and alcohol consumption on T2D risk and related glycaemic traits. Methods and Findings: We conducted both two-sample and one-sample MR to examine the effects of lifetime smoking index (LSI) and alcoholic drinks per week on T2D and continuous traits (fasting glucose, fasting insulin and glycated haemoglobin, HbA1c). For two-sample MR we used results from genome-wide association studies (GWAS) of LSI (N=462,690), alcohol consumption (N=941,280), T2D (N= 148,726 cases and 965,732 controls) and continuous traits (N=149,289 to 209,605). We used inverse variance weighting (IVW) for our main analyses and conducted several sensitivity analyses to explore violation of MR assumptions. We compared two-sample MR to one-sample MR results for alcohol effects on T2D and HbA1c in UK Biobank (N=336,984). Only these analyses were conducted to avoid sample overlap and due to data availability. The main IVW two-sample MR results suggested possible causal effects of higher LSI on T2D risk (OR per 1SD higher LSI=1.42, 95% CI=1.22 to 1.64); however, sensitivity analyses did not consistently support this finding, and there was evidence of potential horizontal pleiotropy. There was no robust evidence that higher drinks per week influenced risk of T2D from our main IVW two-sample MR analyses (OR per 1 SD higher log-transformed drinks per week=1.04, 95% CI=0.40 to 2.65), despite evidence of causal effects on higher fasting glucose (difference in mean fasting glucose in mmol/l per 1SD higher log-transformed drinks per week=0.34, 95% CI=0.09 to 0.59). One-sample MR results suggested a possible causal effect of higher drinks per week on T2D risk (OR per 1 SD higher log-transformed drinks per week=1.71, 95% CI: 1.24 to 2.36), but in contrast, lower HbA1c levels (difference in mean SD of log transformed HbA1c (mol/mol) per 1 SD higher log-transformed drinks per week=-0.07, 95% CI: -0.11 to -0.02). Key limitations include limited generalisability of results due to analyses being conducted in European populations, and potential selection bias in UK Biobank influencing results. Conclusion: Our results suggest effective public health interventions to prevent and/or reduce smoking and alcohol consumption are unlikely to reduce the prevalence of T2D.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leisure-time physical activity, sedentary behavior, and biological aging: evidence from genetic correlation and Mendelian randomization analyses","authors":"Xunying Zhao, Xueyao Wu, Lin He, Jinyu Xiao, Rong Xiang, Linna Sha, Mingshuang Tang, Yu Hao, Yang Qu, Changfeng Xiao, Chenjiarui Qin, Jiaojiao Hou, Qin Deng, Jiangbo Zhu, Sirui Zheng, Jinyu Zhou, Ting Yu, Bin Yang, Xin Song, Tao Han, Jiaqiang Liao, Tao Zhang, Mengyu Fan, Jiayuan Li, Xia Jiang","doi":"10.1101/2024.07.25.24310997","DOIUrl":"https://doi.org/10.1101/2024.07.25.24310997","url":null,"abstract":"Physical inactivity and sedentary behavior are associated with higher risks of age-related morbidity and mortality. However, whether they causally contribute to accelerating biological aging has not been fully elucidated. Utilizing the largest available genome-wide association study (GWAS) summary data, we implemented a comprehensive analytical framework to investigate the causal relationships between moderate-to-vigorous leisure-time physical activity (MVPA), leisure screen time (LST), and four epigenetic age acceleration (EAA) measures: HannumAgeAccel, intrinsic HorvathAgeAccel, PhenoAgeAccel, and GrimAgeAccel. Shared genetic backgrounds across these traits were quantified through genetic correlation analysis. Overall and independent causal effects were assessed through univariable and multivariable Mendelian randomization (MR). A recently developed tissue-partitioned MR approach was further adopted to explore potential tissue-specific pathway that contributes to the observed causal relationships. Among the four EAA measures investigated, consistent results were identified for PhenoAgeAccel and GrimAgeAccel. These two measures were negatively genetically correlated with MVPA (<em>r</em>_g=−0.18~−0.29) and positively genetically correlated with LST (<em>r</em>_g=0.22~0.37). Univariable MR yielded a robust effect of genetically predicted LST on GrimAgeAccel (<em>β</em>_IVW=0.69, <em>P</em>=1.10×10⁻⁷), while MVPA (<em>β</em>_IVW=−1.02, <em>P</em>=1.50×10⁻²) and LST (<em>β</em>_IVW=0.37, <em>P</em>=1.90×10⁻²) showed marginal causal effects on PhenoAgeAccel. Multivariable MR suggested an independent causal role of LST in GrimAgeAccel after accounting for effects of MVPA and other important confounders. Tissue-partitioned MR suggested skeletal muscle tissue associated variants be predominantly responsible for driving the effect of LST on GrimAgeAccel. Findings support sedentary lifestyles as a modifiable causal risk factor in accelerating epigenetic aging, emphasizing the need for preventive strategies to reduce sedentary screen time for healthy aging.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Application of Target Trial Emulation in Vaccine Evaluation: Scoping Review and Recommendations for Future Studies","authors":"Toshiaki Komura, Miwa Watanabe, Kayoko Shioda","doi":"10.1101/2024.07.26.24311066","DOIUrl":"https://doi.org/10.1101/2024.07.26.24311066","url":null,"abstract":"Background: Target trial emulation has gained popularity in evaluating treatments and health interventions. Its application to infectious disease outcomes requires careful consideration, as infectious disease transmission violates the assumption of no interference. We conducted a scoping review to understand how target trial emulation approaches have been applied to vaccine evaluation.\u0000Methods: We conducted a systematic search of literature published in PubMed, Embase, and Web of Science until May 2024, using keywords related to target trial emulation, infectious diseases, and vaccines. Three independent reviewers screened titles and abstracts for relevance. Full-text articles meeting inclusion criteria were further assessed for eligibility. Results: Our search identified 236 studies. Of these, 30 original research studies employed target trial emulation approaches to evaluate vaccines, predominantly published from 2022 to 2024. Most studies (n=28, 93%) were conducted in high-income countries. The majority (n=27, 90%) evaluated the effect of COVID-19 vaccines, with one study each evaluating influenza, MPOX, and rotavirus vaccines. Nationwide healthcare databases were used in 17 studies (57%). Twenty-one studies (70%) conducted analysis among adults aged ≥18 years, while four studies (13%) focused on children &lt;18 years. Most studies did not define the type of vaccine effect they evaluated (e.g., direct, indirect, total, or overall effect), and none incorporated interference in vaccine evaluation.\u0000Discussion: Our review highlights the increasing popularity of target trial emulation in vaccine evaluation following the COVID-19 pandemic. Further discussions are needed to understand how interference can be addressed within this framework.","PeriodicalId":501071,"journal":{"name":"medRxiv - Epidemiology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141778833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}