检索结果-内蒙古大学图书馆

arXiv 2022年

作者： Ektefaie, Yasha Dasoulas, George Noori, Ayush Farhat, Maha Zitnik, Marinka Bioinformatics and Integrative Genomics Program Harvard Medical School BostonMA02115 United States Department of Biomedical Informatics Harvard University BostonMA02115 United States Harvard College CambridgeMA02138 United States Broad Institute of MIT and Harvard CambridgeMA02142 United States Harvard Data Science Initiative CambridgeMA02138 United States Division of Pulmonary and Critical Care Department of Medicine Massachusetts General Hospital BostonMA United States

Artificial intelligence for graphs has achieved remarkable success in modeling complex systems, ranging from dynamic networks in biology to interacting particle systems in physics. However, the increasingly heterogeneous graph datasets call for multimodal methods that can combine different inductive biases—the set of assumptions that algorithms use to make predictions for inputs they have not encountered during training. Learning on multimodal datasets presents fundamental challenges because the inductive biases can vary by data modality and graphs might not be explicitly given in the input. To address these challenges, multimodal graph AI methods combine different modalities while leveraging cross-modal dependencies using graphs. Diverse datasets are combined using graphs and fed into sophisticated multimodal architectures, specified as image-intensive, knowledge-grounded and language-intensive models. Using this categorization, we introduce a blueprint for multimodal graph learning, use it to study existing methods and provide guidelines to design new models. © 2022, CC BY.

关键词： Blueprints

来源：评论

学校读者我要写书评

暂无评论

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children

引用

Pediatric research 2025年第1期97卷 370-377页

作者： Yi-Giien Tsai Chia-Pin Chio Kuender D Yang Ching-Hsiung Lin Yen-Po Yeh Yu-Jun Chang Jien-Wen Chien Shu-Li Wang Shau-Ku Huang Chang-Chuan Chan Department of Pediatrics Changhua Christian Children's Hospital Changhua Taiwan ROC. School of Medicine Kaohsiung Medical University Kaohsiung Taiwan ROC. School of Medicine Chung Shan Medical University Taichung Taiwan ROC. Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan ROC. Department of Medical Research Tungs' Taichung MetroHarbor Hospital Taichung Taiwan ROC. Institute of Environmental and Occupational Health Sciences College of Public Health National Taiwan University Taipei Taiwan ROC. Department of Pediatrics Mackay Memorial Hospital and Department of Microbiology & Immunology National Defense Medical Center Taipei Taiwan ROC. Division of Chest Medicine Department of Internal Medicine Changhua Christian Hospital Changhua Taiwan ROC. Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan ROC. Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan ROC. Department of Recreation and Holistic Wellness MingDao University Changhua Taiwan ROC. Changhua County Public Health Bureau Changhua Taiwan ROC. Epidemiology and Biostatistics Center Changhua Christian Hospital Changhua Taiwan ROC. National Institute of Environmental Health Sciences National Health Research Institutes 35 Keyan Rd Zhunan Miaoli County Miaoli Taiwan ROC. slwang@nhri.edu.tw. National Institute of Environmental Health Sciences National Health Research Institutes 35 Keyan Rd Zhunan Miaoli County Miaoli Taiwan ROC. skhuang@nhri.edu.tw. Johns Hopkins Asthma and Allergy Center School of Medicine Johns Hopkins University Baltimore MD USA. skhuang@nhri.edu.tw. Institute of Environmental and Occupational Health Sciences College of Public Health National Taiwan University Taipei Taiwan ROC. ccchan@ntu.edu.tw.

BACKGROUND:Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS:We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM, NO, and SO was estimated using land-use regression models data on children's school and home addresses. RESULTS:Annual exposure to PM was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM (P < 0.05). An increase of 1 μg/m PM exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO. CONCLUSIONS:Long-term exposures to PM posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT:Annual exposure to PM was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 μg/m annual PM exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of chil

关键词：

来源：评论

学校读者我要写书评

暂无评论

Shotgun Sequencing of Southern Thailand Traditional Sweet Pickled Mango During the Production Process

SSRN

引用

SSRN 2023年

作者： Indrati, Niken Sirisarn, Wanchat Nuanpirom, Jiratchaya Yodsawat, Prasert Wanna, Warapond Prombutara, Pinidphon Phonsatta, Natthaporn Panya, Atikorn Maneerat, Suppasil Poungsombat, Patcha Khoomrung, Sakda Sumpavapol, Punnanee Food Microbiology and Safety Laboratory Food Science and Technology Program Faculty of Agro-Industry Prince of Songkla University Songkhla90110 Thailand Center of Genomics and Bioinformatics Research Faculty of Science Prince of Songkla University Songkhla90110 Thailand Omics Sciences and Bioinformatics Center Faculty of Science Chulalongkorn University Bangkok10330 Thailand Thailand Science Park Pathumthani12120 Thailand Center of Excellence in Innovative Biotechnology for Sustainable Utilization of Bioresources Faculty of Agro-Industry Prince of Songkla University Songkhla90110 Thailand Metabolomics and Systems Biology Department of Biochemistry Faculty of Medicine Siriraj Hospital Mahidol University Bangkok10700 Thailand Siriraj Metabolomics and Phenomics Center Faculty of Medicine Siriraj Hospital Mahidol University Bangkok10700 Thailand Faculty of Science Mahidol University Bangkok10400 Thailand Faculty of Science and Technology Songkhla Rajabhat University Songkhla90000 Thailand

Southern Thailand's traditional sweet pickled mango, known as Ma-Muang Bao Chae-Im (MBC), holds an important place in the local community. Several immersion processes, including brining and submersion in a hypertonic sugar solution, have been employed in the MBC production process. The occurrence of microbial succession during the production process affects its flavor due to the produced metabolites. However, microbial succession during the production process has received inadequate research. Therefore, this study aimed to (i) understand the microbiome alteration and (ii) investigate the functional profiling (metabolic pathways) during MBC production process. Through shotgun metagenomics, the microbial succession was shifting from bacteria in raw mango to fungi in MBC, with Ascomycota as the dominant phylum and Hanseniaspora as the dominant genus in MBC. The abundance of biosynthesis pathways was in line with the occurrence of microbial growth throughout the production process and prolonged storage. Polymyxin resistance was found as a significant pathway during brining 1 (B1-RM) and brining 2 (B2-B1). Mixed acid fermentation pathway and glyoxylate cycle were suggested to have a role in the aroma development of MBC by synthesizing metabolites related to the acidic and alcoholic aroma. © 2023, The Authors. All rights reserved.

关键词： Brining

来源：评论

学校读者我要写书评

暂无评论

Characterization of primary Sjögren's syndrome in the Taiwan Han population through a genome-wide association study and polygenic risk score analysis

引用

Clinical Immunology 2024年 269卷 110381-110381页

作者： Liu, Ting-Yuan Lin, Min-Rou Lu, Hsing-Fang Chen, Yu-Chia Lin, Hui-Ju Chou, Wan-Hsuan Wei, Chun-Yu Palupi, Poppy Diah Liao, Chi-Chou Chang, Yen-Ting Chang, Wei-Chiao Tsai, Fuu-Jen Department of Medical Research China Medical University Hospital China Medical University Taichung 40447 Taiwan Department of Clinical Pharmacy School of Pharmacy Taipei Medical University Taipei 110 Taiwan Department of Ophthalmology Eye Center China Medical University Hospital Taichung 40447 Taiwan Master Program in Clinical Genomics and Proteomics School of Pharmacy Taipei Medical University Taipei 110 Taiwan Core Laboratory of Neoantigen Analysis for Personalized Cancer Vaccine Office of R&D Taipei Medical University Taipei 110 Taiwan Integrative Research Center in Critical Care Wanfang Hospital Taipei Medical University Taipei 116 Taiwan Department of Pharmacy Wan Fang Hospital Taipei Medical University Taipei 110 Taiwan Department of Pharmacology National Defense Medical Center Taipei 110 Taiwan Department of Medical Research China Medical University Hospital Taichung 40402 Taiwan School of Chinese Medicine China Medical University Taichung 40402 Taiwan Division of Pediatric Medical Genetics Children's Hospital of China Medical University Taichung 40447 Taiwan Department of Biotechnology and Bioinformatics Asia University Taichung 41354 Taiwan

Background: Sjögren's syndrome (SS) is an autoimmune disorder that primarily affects the exocrine glands, leading to dryness of mucous membranes and systemic manifestations. This study aimed to identify genetic markers associated with primary SS (pSS) in the Taiwan Han population through a hospital-based genome-wide association study (GWAS) and polygenic risk score (PRS) analysis, addressing the lack of genetic research. Results: This study included 11,390 patients diagnosed with pSS and 113,900 controls. GWAS identified one known locus and eight novel loci. Known HLA alleles, including HLA-DRB1*15:01 and HLA-DQA1*03:01, were successfully replicated in a consistent effect direction. PRS analysis revealed that several autoimmune diseases share similar genetic backgrounds with pSS, including rheumatoid arthritis and systemic lupus erythematosus. Conclusion: This study represents the largest cohort to date on the genetics of pSS in the Taiwan Han population. Our findings provide valuable insights into the pathogenesis of pSS and emphasize the comorbidities associated with it as an autoimmune disease. © 2024

关键词： Gene polymorphism Genome-wide association study (GWAS) Human leukocyte antigen (HLA) Phenome-wide association study (PheWAS) Polygenic risk score (PRS) Sjögren's syndrome

来源：评论

学校读者我要写书评

暂无评论

Clinical Features and Outcomes of Primary Breast Diffuse Large B-Cell Lymphoma: A Matched-Pair Study

引用

Clinical medicine Insights: Oncology 2023年 17卷

作者： Teng, Ling-Chiao Liao, Yu-Min Gau, Jyh-Pyng Hsiao, Tzu-Hung Chen, Tsung-Chih Chen, Mei-Hui Yeh, Su-Peng Teng, Chieh-Lin Jerry Division of Hematology/Medical Oncology Department of Medicine Taichung Veterans General Hospital Taichung Taiwan Department of Hematology and Oncology China Medical University Hospital Taichung Taiwan Division of Hematology and Oncology Department of Medicine Taipei Medical University Hospital Taipei City Taiwan Department of Medical Research Taichung Veterans General Hospital Taichung Taiwan Department of Chemical Engineering National Tsing Hua University Hsinchu Taiwan Department of Public Health Fu Jen Catholic University New Taipei City Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan Department of Nursing Taichung Veterans General Hospital Taichung Taiwan College of Nursing Hung Kuang University Taichung Taiwan School of Medicine China Medical University Taichung Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Department of Life Science Tunghai University Taichung Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan

Background: The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. Methods: This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Results: Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P =.206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%;P =.772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14;95% CI: 0.66-6.96;P =.206) and OS (HR: 1.26;95% CI: 0.27-5.93;P =.772). Conclusion: Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required. © The Author(s) 2023.

关键词： breast DLBCL NGS OS PFS

来源：评论

学校读者我要写书评

暂无评论

Revelation of potential antiviral activity of Azadirachta indica against Zika virus protease: An integrated molecular docking and dynamic simulation approach

Computational and Structural Biotechnology Reports

引用

Computational and Structural Biotechnology Reports 2025年 2卷

作者： Md. Habib Ullah Masum Rehana Parvin Syed Mohammad Lokman Zarin Tasnim Md. Mazharul Alam Jannatul Ferdous Department of Genomics and Bioinformatics Faculty of Biotechnology and Genetic Engineering Chattogram Veterinary and Animal Sciences University Khulshi 4225 Bangladesh Department of Pathology and Parasitology Faculty of Veterinary Medicine Chattogram Veterinary and Animal Sciences University Khulshi 4225 Bangladesh Asian University for Women (AUW) Chattogram 4000 Bangladesh Department of Industrial Biotechnology Faculty of Biotechnology and Genetic Engineering Chattogram Veterinary and Animal Sciences University Khulshi 4225 Bangladesh Functional Genomics and Proteomics Laboratory (FGPL) Department of Genetic Engineering and Biotechnology Faculty of Biological Sciences University of Chittagong Chattogram 4331 Bangladesh Department of Obstetrics and Gynecology Chittagong Medical College Hospital Chattogram 4203 Bangladesh

The Zika virus (ZIKV) is an RNA virus that mostly affects humans and primates and is transmitted via Aedes mosquitoes . The emergence of ZIKV has intensified global health concerns, emphasizing the urgent need for effective antiviral therapies. As a vital enzyme in the replication of ZIKV, the NS2B-NS3 protease offers a promising therapeutic target. This study leverages computer-aided drug design to identify bioactive compounds capable of inhibiting the ZIKV NS2B-NS3 protease, thereby disrupting viral replication. Bioactive compounds from Azadirachta indica were screened through virtual approaches, resulting in six with exceptional docking scores (<-5.5 kcal/mol). Analyses of the physicochemical properties validated the drug-like traits of the IMPHY014854 and IMPHY014908, conveying suitable hydrogen bonding profiles and moderate solubility (Log S: −2.22 to −3.60). Evaluations of pharmacokinetics suggested significant gastrointestinal absorption while exposing no permeability across the blood-brain barrier, thereby reducing interactions with the central nervous system. Toxicity evaluations revealed limited toxic effects, while several bioactive compounds exhibited particular toxicological issues. Molecular dynamics simulations further revealed the stability and interaction dynamics of ZIKV protease-ligand complexes, where the IMPHY014854 and IMPHY014908 exhibited significant residue flexibility, compactness, and solvent accessibility profiles over a 100 ns simulation. Principal component analysis revealed conformational distinctions, while Gibbs's free energy analysis demonstrated greater stability for the ZIKV protease-IMPHY014908 complex. This integrative computational strategy highlights the potential of phytochemicals as the ZIKV protease inhibitors and provides a foundation for developing effective antiviral drugs. Further, in vivo studies must be implemented to validate these findings and advance therapeutic prospects against ZIKV.

关键词： Mosquito-borne Phytodynamics Biocomputational Neem plant Protease inhibitor Antiviral drug

来源：评论

学校读者我要写书评

暂无评论

Weight, habitual fibre intake, and microbiome composition predict tolerance to fructan supplementation

引用

Journal of Plant Foods 2024年第6期75卷

作者： Jeffrey Letourneau Benjamin C. Neubert Diana Dayal Verónica M. Carrion Heather K. Durand Eric P. Dallow Sharon Jiang Michelle Kirtley Geoffrey S. Ginsburg P. Murali Doraiswamy Lawrence A. David a Department of Molecular Genetics and Microbiology Duke University School of Medicine Durham NC USA b Program in Computational Biology and Bioinformatics Duke University School of Medicine Durham NC USA c School of Medicine University of North Carolina Chapel Hill NC USA d Duke Office of Clinical Research Duke University Durham NC USA e Duke Center for Applied Genomics and Precision Medicine Duke University Health System Durham NC USAf Department of Medicine Duke University School of Medicine Durham NC USA e Duke Center for Applied Genomics and Precision Medicine Duke University Health System Durham NC USAf Department of Medicine Duke University School of Medicine Durham NC USAg Department of Psychiatry Duke University School of Medicine Durham NC USAh Duke Microbiome Center Duke University School of Medicine Durham NC USA a Department of Molecular Genetics and Microbiology Duke University School of Medicine Durham NC USAb Program in Computational Biology and Bioinformatics Duke University School of Medicine Durham NC USAh Duke Microbiome Center Duke University School of Medicine Durham NC USA

Fructans are commonly used as dietary fibre supplements for their ability to promote the growth of beneficial gut microbes. However, fructan consumption has been associated with various dosage-dependent side effects. We characterised side effects in an exploratory analysis of a randomised trial in healthy adults (n= 40) who consumed 18 g/day inulin or placebo. We found that individuals weighing more or habitually consuming higher fibre exhibited the best tolerance. Furthermore, we identified associations between gut microbiome composition and host tolerance. Specifically, higher levels ofChristensenellaceae R-7 groupwere associated with gastrointestinal discomfort, and a machine-learning-based approach successfully predicted high levels of flatulence, with[Ruminococcus] torques groupand (Oscillospiraceae)UCG-002 *** as key predictive taxa. These data reveal trends that can help guide personalised recommendations for initial inulin dosage. Our results support prior ecological findings indicating that fibre supplementation has the greatest impact on individuals whose baseline fibre intake is lowest.

关键词： Microbiome inulin dietary fibre gastroenterology bioinformatics

来源：评论

学校读者我要写书评

暂无评论

Author Correction: SARS-CoV-2 infection engenders heterogeneous ribonucleoprotein interactions to impede translation elongation in the lungs

引用

EXPERIMENTAL AND MOLECULAR medicine 2023年第12期55卷 2609-2609页

作者： Kim, Junsoo Youn, Daehwa Choi, Seunghoon Lee, Youn Woo Sumberzul, Dulguun Yoon, Jeongeun Lee, Hanju Bae, Jong Woo Noh, Hyuna On, Dain Hong, Seung-Min An, Se-Hee Jang, Hui Jeong Kim, Seo Yeon Kim, Young Been Hwang, Ji-Yeon Lee, Hyo-Jung Kim, Hong Bin Park, Jun Won Yun, Jun-Won Shin, Jeon-Soo Seo, Jun-Young Nam, Ki Taek Choi, Kang-Seuk Lee, Ho-Young Chang, Hyeshik Seong, Je Kyung Cho, Jun Center for RNA Research Institute for Basic Science (IBS) Seoul National University Seoul Republic of Korea Interdisciplinary Program in Bioinformatics Seoul National University Seoul Republic of Korea Department of Biomedical Science and Engineering Gwangju Institute of Science and Technology (GIST) Gwangju Republic of Korea Korea Mouse Phenotyping Center (KMPC) Seoul National University Seoul Republic of Korea Laboratory of Developmental Biology and Genomics Research Institute for Veterinary Science and BK 21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Republic of Korea Department of Nuclear Medicine Seoul National University Bundang Hospital Seongnam Republic of Korea School of Biological Sciences Seoul National University Seoul Republic of Korea Laboratory of Avian Diseases Research Institute for Veterinary Science and BK 21 PLUS Program for Creative Veterinary Science Research College of Veterinary Medicine Seoul National University Seoul Republic of Korea Preclinical Research Center Seoul National University Bundang Hospital Seongnam Republic of Korea Department of Periodontology Section of Dentistry Seoul National University Bundang Hospital Seongnam Republic of Korea Department of Internal Medicine Seoul National University Bundang Hospital Seoul National University College of Medicine Seongnam Republic of Korea Division of Biomedical Convergence College of Biomedical Science Kangwon National University ChunCheon Republic of Korea Laboratory of Veterinary Toxicology College of Veterinary Medicine Seoul National University Seoul Republic of Korea Severance Biomedical Science Institute Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine Seoul Republic of Korea Department of Nuclear Medicine Seoul National University College of Medicine Seoul Republic of Korea Interdisciplinary Program and BIO MAX Institute Seoul National University

来源：评论

学校读者我要写书评

暂无评论

Adverse Health Correlates of Intimate Partner Violence against Older Women: Mining Electronic Health Records

arXiv

引用

arXiv 2022年

作者： Yılmaz, Serhan Günay, Erkan Lee, Da Hee Whiting, Kathleen Silver, Kristen Koyutürk, Mehmet Karakurt, Günnur Case Western Reserve University Department of Computer and Data Sciences ClevelandOH44106 United States Şişli Hamidiye Etfal Training and Research Hospital Emergency Department Istanbul35371 Turkey Des Moines University Osteopathic Medicine and Public Health Des MoinesIA50312 United States Uniformed Services University Neuroscience Program WashingtonDC20814 United States University of Akron Department of Psychology AkronOH44325 United States Case Western Reserve University Center for Proteomics & Bioinformatics ClevelandOH44106 United States Case Western Reserve University Department of Psychiatry ClevelandOH44106 United States University Hospitals Family Medicine ClevelandOH44106 United States

Intimate partner violence (IPV) is often studied as a problem that predominantly affects younger women. However, studies show that older women are also frequently victims of abuse even though the physical effects of abuse are harder to detect. In this study, we mined the electronic health records (EHR) available through IBM Explorys to identify health correlates of IPV that are specific to older women. Our analyses suggested that diagnostic terms that are co-morbid with IPV in older women are dominated by substance abuse and associated toxicities. When we considered differential co-morbidity, i.e., terms that are significantly more associated with IPV in older women compared to younger women, we identified terms spanning mental health issues, musculoskeletal issues, neoplasms, and disorders of various organ systems including skin, ears, nose and throat. Our findings provide pointers for further investigation in understanding the health effects of IPV among older women, as well as potential markers that can be used for screening IPV. © 2022, CC BY-NC-SA.

关键词： Records management

来源：评论

学校读者我要写书评

暂无评论

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

引用

Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

关键词：

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：