利用“All of Us”研究计划245,388例全基因组序列及英国生物银行数据，针对32项性状和疾病构建多祖先多基因风险评分，并在“All of Us”多祖先参与者中评估祖先背景、方法和遗传结构对评分性能的影响。结果显示，增加“All of Us”多样性可提高若干性状的评分准确性，尤其在代表性不足人群中；但将“All of Us”与英国生物银行荟萃分析以最大化样本量并非普遍最优，对多基因性较低的性状，仅用“All of Us”训练在非洲祖先参与者中表现最佳，提示祖先富集效应。个体评分准确性随与发现全基因组关联研究祖先分歧增加而线性下降，多祖先训练数据可减弱该衰减。结论强调，更具代表性的生物样本库有助于实现公平的多基因风险评分性能。
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完整作者
Kristin Tsuo、Zhuozheng Shi、Tian Ge、Ravi Mandla、Kangcheng Hou、Yi Ding、Bogdan Pasaniuc、Ying Wang、Alicia R Martin
作者机构
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. ktsuo@broadinstitute.org.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ktsuo@broadinstitute.org.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ktsuo@broadinstitute.org.
Graduate Program in Genomics and Computational Biology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Division of Population Sciences, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. yiwang@broadinstitute.org.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. yiwang@broadinstitute.org.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. yiwang@broadinstitute.org.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. armartin@broadinstitute.org.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. armartin@broadinstitute.org.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. armartin@broadinstitute.org.
技术路线
数据/样本：All of Us研究项目245,388例全基因组序列与UK Biobank数据；分析：开发32个性状/疾病的多祖先多基因风险评分（PRS），评估祖先背景、方法学和遗传结构对AoU参与者PRS性能的影响。
Simultaneous derivation, validation, and comparison of predictor hazard ratios for cardiovascular risk prediction equations in patients with diabetes from high versus non-high income countries: cohort study.
Section of Epidemiology and Biostatistics, School of Population Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Department of Chronic Diseases and Health Promotion, Yinzhou District Centre for Disease Control and Prevention, Ningbo, China.
Department of General Practice and Primary Health Care, School of Population Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Medicine, School of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Ngāi Tahu Māori Health Research Unit, Division of Health Sciences, University of Otago, Dunedin, New Zealand.
Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China peigao@bjmu.edu.cn.
Peking University Clinical Research Institute, Peking University, Beijing, China.
Fei Liu、Kai Wang、Hui Xu、Cheng Tang、Xian Shen、Meihao Wang、Lei Yang、Li Yang、Li Liu、Changxi Hu、Gen Li、Wei Wu、Zixing Zou、Bingzhou Li、Sian Liu、Jin Kang、Jungho Kong、Ting Li、Io Nam Wong、Xiaoying Huang、Gang Chen、Wenyang Lu、Ian Ziyar、Charlotte L Zhang、Yiwen Sun、Weihong Lin、Caiwen Ou、Manson Fok、Taiwa Hou、Winston Wang、Kanmin Xue、Yun Yin、Hao Zhu、Jonathan Gootenberg、Omar O Abudayyeh、Michael Karin、Alexandre Loupy、John E J Rasko、Trey Ideker、Huiyan Luo、Eric Oermann、Kang Zhang、International Consortium of Digital Twins in Healthcare and Medicine
作者机构
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Department of Urology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Guangzhou National Laboratory, Guangzhou, China.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Department of General Surgery, Department of Hepatobiliary Surgery, Zhejiang-Germany Interdisciplinary Joint Laboratory of Hepatobiliary-Pancreatic Tumor and Bioengineering, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Radiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Intelligent Medical Imaging of Wenzhou, Healthcare Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Orthopedics, Key Laboratory of Hepatosplenic Surgery of Ministry of Education, the First Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Respiratory and Critical Care Medicine, Center for Big Data and Intelligent Medicine, the First Affiliated Hospital of Chongqing Medical University, Key Laboratory of Digital Health and Intelligent Medicine, Chongqing Municipal Health Commission, Chongqing Translational Medicine Center, Chongqing, China.
Department of Health Management, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Big Data and Biomedical AI, College of Future Technology, Peking University, Peking-Tsinghua Center for Life Sciences, Beijing, China.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Guangzhou National Laboratory, Guangzhou, China.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China.
Departments of Medicine and Bioengineering, Moores Cancer Center, School of Medicine, UC San Diego, CA, USA.
Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdisciplinary and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, China.
Nepean Hospital, Sydney, Australia.
Key Laboratory of Intelligent Medical Imaging of Wenzhou, Healthcare Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Dongguan Hospital, Southern Medical University, Guangzhou, China.
Conde S. Januario Hospital, Macau, China.
Department of Internal Medicine, Mayo Clinic, Arizona, USA.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Faculty of Health and Wellness, Faculty of Business, City University of Macau, Taipa, Macau SAR, China.
Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Gene and Cell Therapy Institute, Mass General Brigham, Cambridge, MA, USA.
Université Paris Cité, INSERM U970 PARCC, Paris Institute for Transplantation and Organ Regeneration, F-75015 Paris, France; Department of Kidney Transplantation, Assistance Publique - Hôpitaux de Paris, Paris, France.
Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
Departments of Medicine and Bioengineering, Moores Cancer Center, School of Medicine, UC San Diego, CA, USA; Big Data Institute, Oxford University, Oxford, UK.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Departments of Neurosurgery, Radiology, and Data Science, Neuroscience Institute, NYU Langone Medical Center, New York University, New York, NY, USA.
Clinical Data Science Institute, State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, and The Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China; Artificial Intelligence Cross Disciplinary Research Institute, Faculty of Medicine, Macau University of Science and Technology, Macau, China; Guangzhou National Laboratory, Guangzhou, China; State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, China. Electronic address: kang.zhang@gmail.com.
技术路线
3.67 million individuals/17.7 million clinical visits (COMPASS cohort, longitudinal EHR + chest X-ray) → Oncoformer unified multimodal transformer analysis → validation on independent external cohorts including UK Biobank, with staging independently validated against postoperative pathological endpoints and convergence on core cancer genomic pathways
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