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公共数据库综述Nature genetics

Genome-wide analyses identify 60 loci associated with liver triglyceride content.

0 次引用趋势数据不足

研究对来自英国生物银行的71,488名欧洲血统参与者的磁共振成像衍生肝脏甘油三酯含量进行了大规模全基因组关联研究荟萃分析,样本量约为既往研究的2倍。共识别60个独立位点,其中31个为新发现;肝脏甘油三酯含量的单核苷酸多态性遗传率估计为25%。整合精细定位与基因优先排序分析为48个位点提名了候选效应基因。31个新发现变异中有14个在临床诊断的代谢功能障碍相关脂肪性肝病荟萃分析(42,163例病例和1,646,254例对照)中得到验证。肝脏甘油三酯含量多基因风险评分最高十分位者较最低十分位者肝硬化风险高2.71倍,肝细胞癌风险高7.47倍。与多基因风险评分相关的血浆蛋白富集于代谢重塑和炎症通路,遗传风险越高,肝脏富集蛋白特征越强,内脏脂肪特征越弱。研究细化了肝脏甘油三酯含量的遗传结构,将多基因易感性同下游代谢与炎症通路联系起来,为脂肪性肝病的遗传基础提供了见解。

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完整作者

Oveis Jamialahmadi、Shahir Mowlaei、Kyla Z Gelev、Rosellina M Mancina、Valentina Flagiello、Julia Kozlitina、Päivi Pajukanta、Luca Valenti、Stefano Romeo

作者机构

  • Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden. oveis.jamialahmadi@ki.se.
  • Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden.
  • Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy.
  • Operative Research Unit of Clinical Medicine and Hepatology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
  • The Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA.
  • Institute for Precision Health, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
  • Precision Medicine and Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
  • Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden. stefano.romeo@ki.se.
  • Department of Endocrinology, Karolinska University Hospital, Huddinge, Sweden. stefano.romeo@ki.se.
  • Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy. stefano.romeo@ki.se.
  • Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. stefano.romeo@ki.se.
  • Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. stefano.romeo@ki.se.

技术路线

MRI衍生肝脏甘油三酯含量数据(71,488名欧洲 ancestry UK Biobank参与者)→全基因组关联研究荟萃分析→识别60个独立位点(31个新位点)并估计SNP遗传力为25%→整合精细定位与基因优先级分析提名48个位点的候选效应基因→在临床诊断的代谢功能障碍相关脂肪性肝病荟萃分析(42,163例病例和1,646,254例对照)中验证31个新位点中的14个→多基因风险评分与肝硬化(OR 2.71)和肝细胞癌(OR 7.47)风险关联分析→与多基因风险评分相关的血浆蛋白通路富集分析(代谢重塑和炎症通路,肝脏富集蛋白特征增加、内脏脂肪特征减少)

最近 5 个完整年度引用趋势

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不含 2026 年,仅展示最近 5 个完整年度。

数据来源:openalex更新时间:2026/10/29 12:36
公共数据库综述Frontiers in genetics

Revisiting the genetic support of leukotriene pathway drug targets in atherosclerotic cardiovascular disease.

0 次引用趋势数据不足

一项基于英国生物银行378,962名参与者的多祖先荟萃分析,重新评估了花生四烯酸5-脂氧合酶(由ALOX5编码)及其激活蛋白(由ALOX5AP编码)与动脉粥样硬化性心血管疾病(ASCVD)的遗传关联。研究刻画了既往所研究的ALOX5和ALOX5AP多态性的祖先差异,这些差异可能导致人群分层。在充分校正祖先背景后,既往报道的关联未能重现。此外,关联扫描和转录组范围关联研究结果整体不支持白血球三烯通路基因变异参与ASCVD风险,亦不支持ALOX5或其激活蛋白的遗传变异在ASCVD风险中发挥作用。

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最近 5 个完整年度引用趋势

0110202102022020230202402025

不含 2026 年,仅展示最近 5 个完整年度。

数据来源:openalex更新时间:2026/11/02 07:00
公共数据库综述Frontiers in immunology

GlycoRNA-related cellular program scoring identifies Siglec- and myeloid-associated tumor microenvironments for glycoRNA validation.

0 次引用趋势数据不足

糖基化RNA(glycoRNA)是RNA生物学与细胞表面糖生物学之间的新联系,但其与人类肿瘤的相关性尚不明确。研究团队基于文献证据构建了涵盖RNA身份、N-聚糖与唾液酸化通路、RNA转运及凝集素/Siglec识别的基因模块,并建立表达-based复合评分——glycoRNA相关细胞程序评分,用于在大型肿瘤队列中优先筛选适合实验验证的肿瘤情境。该评分应用于TCGA 32种癌症类型的9,186例肿瘤,并结合临床变量、白细胞分数、免疫特征及Siglec/检查点/髓系轴评分分析。结果显示,胃腺癌、胶质母细胞瘤、肺腺癌、食管癌、间皮瘤、胰腺癌、乳腺癌和肺鳞癌等肿瘤类型评分较高;校正年龄、性别、分期和肿瘤类型后,生存分析未显示稳健的FDR显著关联。去除免疫和Siglec相关基因后的敏感性分析中,评分仍与Siglec解码器、髓系、检查点及整合生态位特征相关。胶质母细胞瘤单细胞和空间分析显示,高评分见于肿瘤、髓系、间充质及生态位相关区域。研究提示,glycoRNA相关转录程序倾向于发生在免疫和髓系富集的肿瘤微环境中,尤其涉及Siglec相关特征,为后续生化、影像、空间和扰动实验验证提供了优先肿瘤情境。

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最近 5 个完整年度引用趋势

0110202102022020230202402025

不含 2026 年,仅展示最近 5 个完整年度。

数据来源:openalex更新时间:2026/11/01 02:24
公共数据库综述Nature genetics

Genome-wide association analyses of borderline personality disorder identify 11 loci and highlight shared risk with mental and somatic disorders.

1 次引用趋势数据不足

研究纳入欧洲血统的12339例患者和1041717名对照进行发现阶段分析,并在685例患者和107750名对照中重复验证,开展迄今规模最大的边缘型人格障碍全基因组关联研究荟萃分析。结果识别出11个独立相关基因组位点和9个风险基因;单核苷酸多态性遗传率为17.3%,构建的多基因评分在责任量表上可解释4.6%的表型变异。边缘型人格障碍与创伤后应激障碍、抑郁、注意缺陷多动障碍、反社会行为及自杀和自伤相关指标的全基因组关联研究显示最强的正向遗传相关性。基于多基因评分在生物样本库中开展的全表型组分析证实上述关联,并发现其与阻塞性肺疾病和糖尿病等其他疾病相关。分析表明边缘型人格障碍是一种多基因疾病,其遗传风险与精神和躯体健康状况存在显著重叠。

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AI 辅助短评,基于标题和摘要整理

该研究通过迄今最大规模BPD全基因组关联荟萃分析,识别11个独立位点与9个风险基因,并量化其多基因结构及遗传重叠。其价值在于以PGS跨生物库验证,将BPD遗传风险与精神及躯体疾病(如肺病、糖尿病)联系起来,为共病机制研究提供遗传学线索。

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完整作者

Fabian Streit、Swapnil Awasthi、Alisha S M Hall、Alice Braun、Maria Niarchou、Eirini Marouli、Oladapo Babajide、Josef Frank、Lea Zillich、Carolin M Callies、Diana Avetyan、Eric Zillich、Joonas Naamanka、Jean Gonzalez、Arvid Harder、Yi Lu、Zouhair Aherrahrou、Zain-Ul-Abideen Ahmad、Helga Ask、Anthony Batzler、Michael E Benros、Odette M Brand-de Wilde、Søren Brunak、Mie T Bruun、Lea A N Christoffersen、Lucía Colodro-Conde、Brandon J Coombes、Elizabeth C Corfield、Norbert Dahmen、Maria Didriksen、Khoa M Dinh、Srdjan Djurovic、Joseph Dowsett、Ole Kristian Drange、Helene Dukal、Susanne Edelmann、Christian Erikstrup、Mariana K Espinola、Eva Fassbinder、Annika Faucon、Diana S Ferreira de Sá、Jerome C Foo、Maria Gilles、Alfonso Gutiérrez-Zotes、Thomas F Hansen、Magnus Haraldsson、R Patrick Harper、Alexandra Havdahl、Urs Heilbronner、Stefan Herms、Henrik Hjalgrim、Christopher Hübel、Gitta A Jacob、Bitten Aagaard、Anders Jorgensen、Martin Jungkunz、Nikolaus Kleindienst、Nora Knoblich、Stefanie Koglin、Julia Kraft、Kristi Krebs、Christopher W Lee、Yuhao Lin、Stefanie Lis、Amanda Lisoway、Ioannis A Malogiannis、Amy Martinsen、Tolou Maslahati、Katharina Merz、Andreas Meyer-Lindenberg、Susan Mikkelsen、Christina Mikkelsen、Arian Mobascher、Gerard Muntané、Asmundur Oddsson、Sisse R Ostrowski、Teemu Palviainen、Ole B V Pedersen、Geir Pedersen、Liam Quinn、Matthias A Reinhard、Florian A Ruths、Björn H Schott、Michael Schredl、Emanuel Schwarz、Cornelia E Schwarze、Michael Schwinn、Tabea Sarah Send、Engilbert Sigurdsson、Katja Simon-Keller、Astros T Skuladottir、Joaquim Soler、Anne Sonley、Erik Sørensen、Hreinn Stefansson、Peter Straub、Jaana Suvisaari、Martin Tesli、Jacob Træholt、Henrik Ullum、Maja P Völker、G Bragi Walters、Rujia Wang、Christian C Witt、Gerhard Zarbock、Peter Zill、John-Anker Zwart、DBDS Genomic Consortium、GLAD Study、HUNT All-In Psychiatry、Ole A Andreassen、Arnoud Arntz、Joanna M Biernacka、Martin Bohus、Gerome Breen、Alexander L Chapman、Sven Cichon、Lea K Davis、Michael Deuschle、Sebastian Euler、Sabine C Herpertz、Benjamin Hummelen、Andrea Jobst、Jaakko Kaprio、James L Kennedy、Kelli Lehto、Klaus Lieb、Lourdes Martorell、Shelley McMain、Richard Musil、Vanessa Nieratschker、Markus M Nöthen、Frank Padberg、Aarno Palotie、Juan C Pascual、Nader Perroud、Josep A Ramos-Quiroga、Ted Reichborn-Kjennerud、Marta Ribases、Stefan Roepke、Dan Rujescu、Sandra Sanchez-Roige、Claudia Schilling、Christian Schmahl、Kari Stefansson、Thorgeir E Thorgeirsson、Gustavo Turecki、Elisabet Vilella、Thomas Werge、Bendik S Winsvold、Johannes Wrege、Marcella Rietschel、Stephan Ripke、Stephanie H Witt

作者机构

  • Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. fabian.streit@zi-mannheim.de.
  • Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. fabian.streit@zi-mannheim.de.
  • Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. fabian.streit@zi-mannheim.de.
  • German Center for Mental Health (DZPG), Partner Site Mannheim-Heidelberg-Ulm, Mannheim-Heidelberg-Ulm, Germany. fabian.streit@zi-mannheim.de.
  • Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
  • Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Department of Affective Disorders, Aarhus University Hospital-Psychiatry, Aarhus, Denmark.
  • Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University London, London, UK.
  • Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • German Center for Mental Health (DZPG), Partner Site Mannheim-Heidelberg-Ulm, Mannheim-Heidelberg-Ulm, Germany.
  • Hector Institute for Translational Brain Research, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Health Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.
  • Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
  • DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany.
  • University Heart Center Lübeck, Lübeck, Germany.
  • Social, Genetic and Developmental Psychiatry Centre, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK.
  • PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway.
  • PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
  • Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
  • Copenhagen Research Centre for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
  • Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Netherlands Institute for Personality Disorders, Halsteren, Netherlands.
  • Department of Public Health & Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
  • Department of Clinical Immunology, Zealand University Hospital, Køge, Denmark.
  • Institute of Biological Psychiatry, Mental Health Services, University of Copenhagen, Copenhagen, Denmark.
  • Brain and Mental Health Research Program, QIMR Berghofer, Brisbane, Queensland, Australia.
  • School of Psychology, The University of Queensland, Brisbane, Queensland, Australia.
  • Psychiatric Genetic Epidemiology Group, Research Department & Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
  • MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Department of Psychiatry and Psychotherapy, University Medical Center, University of Mainz, Mainz, Germany.
  • Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
  • Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
  • Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Department of Psychiatry, Sørlandet Hospital, Kristiansand, Agder, Norway.
  • Department of Psychiatry and Psychotherapy, University Hospital Tübingen, Tübingen, Germany.
  • German Center for Mental Health (DZPG), partner site Tübingen, Tübingen, Germany.
  • Department of Psychiatry and Psychotherapy, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.
  • Department of Psychology, Division of Clinical Psychology and Psychotherapy, Saarland University, Saarbrücken, Germany.
  • Institute for Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Hospital Universitari Institut Pere Mata (HUIPM), Institute de Recerca Biomédica Catalunya Sud (IRB-CatSud) previously IISPV-CERCA, Universitat Rovira i Virgili (URV), Reus, Spain.
  • Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
  • Neurogenomic, Translational Research Centre, Copenhagen University Hospital, Glostrup, Denmark.
  • Danish Headache Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Landspitali University Hospital, Reykjavik, Iceland.
  • Faculty of Medicine, Department of Psychiatry, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
  • Bradford District Care NHS Foundation Trust, Bradford, UK.
  • Institute of Psychiatric Phenomics and Genomics (IPPG), LMU University Hospital, LMU Munich, Munich, Germany.
  • Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Institute of Human Genetics, University Hospital Bonn & University of Bonn, Bonn, Germany.
  • Danish Cancer Institute, Copenhagen, Denmark.
  • Department of Haematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • UK National Institute for Health Research (NIHR) Biomedical Research Centre, South London and Maudsley Hospital and King's College London, London, UK.
  • National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
  • Clinic for Child and Adolescent Psychiatry, German Red Cross Hospitals Westend, Berlin, Germany.
  • Institute for Psychology, Department of Clinical Psychology and Psychotherapy, University of Freiburg, Freiburg, Germany.
  • Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
  • Psychiatric Center Copenhagen, Copenhagen, Denmark.
  • Institute for Medical and Data Ethics, Heidelberg University, Faculty of Medicine, Heidelberg, Germany.
  • German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry and Neurosciences, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany.
  • Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
  • Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
  • Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • First Department of Psychiatry, Eginition Hospital Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  • Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
  • Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • Department of Psychiatry and Psychotherapy, LMU University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.
  • Institut de Biologia Evolutiva (UPF-CSIC), Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain.
  • deCODE genetics / AMGEN, Reykjavik, Iceland.
  • Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • Department of Research and Innovation, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • German Center for Mental Health (DZPG), Partner Site Munich-Augsburg, Munich-Augsburg, Germany.
  • South London and Maudsley NHS Foundation Trust, London, UK.
  • Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
  • German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
  • Leibniz Institute for Neurobiology, Magdeburg, Germany.
  • Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany.
  • Department of Psychiatry and Psychotherapy, Sleep Laboratory, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Clinical Psychology and Psychotherapy, Charlotte Fresenius University, Wiesbaden, Germany.
  • Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain.
  • Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Department of Psychiatry and Forensic Medicine & Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain.
  • Borderline Personality Disorder Clinic, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
  • Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
  • Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
  • Mental health and suicide, Norwegian Institute of Public Health, Oslo, Norway.
  • Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Statens Serum Institut, Copenhagen, Denmark.
  • Department of Anaesthesiology and Operative Intensive Care, University Hospital Mannheim, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
  • IVAH, Institut für Verhaltenstherapie-Ausbildung Hamburg, gemeinnützige GmbH, Hamburg, Germany.
  • KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
  • Department of Clinical Psychology, University of Amsterdam, Amsterdam, the Netherlands.
  • Department of Psychiatry & Psychology, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
  • Department of Psychology, Faculty of Arts and Social Sciences, Simon Fraser University, Vancouver, British Columbia, Canada.
  • DBT Centre of Vancouver, Vancouver, British Columbia, Canada.
  • Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany.
  • Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Department of Consultation Psychiatry and Psychosomatics, University Hospital Zurich, Zurich, Switzerland.
  • Department of General Psychiatry, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.
  • Borderline Personality Disorder Clinic, General Adult Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
  • Oberberg Fachkliniken for Psychiatry, Psychosomatics and Psychotherapy, Bad Tölz, Germany.
  • Insitute of Human Genetics, University Hospital Bonn & University of Bonn, Bonn, Germany.
  • Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
  • The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mental Health and Psychiatry Department, Vic Hospital Consortium, Vic, Spain.
  • Department of Psychiatric, University Hospitals of Geneva, Geneva, Switzerland.
  • Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
  • Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
  • Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
  • Department of Psychiatry, Oberberg Fachkliniken for Psychiatry, Psychosomatics and Psychotherapy, Wendisch Rietz, Germany.
  • Department of Psychiatry, University of Halle, Halle, Germany.
  • Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
  • Douglas Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
  • Department of Neurology, Oslo University Hospital, Oslo, Norway.
  • Medical Faculty, University of Basel, Basel, Switzerland.
  • Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. stephanie.witt@zi-mannheim.de.
  • German Center for Mental Health (DZPG), Partner Site Mannheim-Heidelberg-Ulm, Mannheim-Heidelberg-Ulm, Germany. stephanie.witt@zi-mannheim.de.

技术路线

12,339例病例与1,041,717例对照的发现样本及685例病例与107,750例对照的重复样本(均为欧洲 ancestry)→GWAS荟萃分析(识别11个独立位点、9个基于基因分析的风险基因、SNP遗传力17.3%、构建多基因评分PGS,解释4.6%的责任尺度表型方差)→在Vanderbilt大学医学中心Biobank和UK Biobank中进行PGS的表型组关联分析验证

最近 5 个完整年度引用趋势

0110202102022020230202402025

不含 2026 年,仅展示最近 5 个完整年度。

数据来源:openalex更新时间:2026/11/01 03:56
公共数据库基础研究Nature

Genetic analysis of circulating metabolic traits in 619,372 individuals.

6 次引用趋势数据不足

一项针对循环代谢特征的遗传分析研究,在爱沙尼亚生物样本库和英国生物样本库中,对多达619,372名个体的249项循环代谢特征进行了全基因组关联分析(GWAS)荟萃分析。研究从8,398个基因座中识别出88,127个常见及低频基因座-特征关联,这些关联集中于共享的基因和通路。通过统计精细定位、系统性全表型共定位和顺式孟德尔随机化,研究者探索了代谢特征与疾病结局之间可能的因果联系。研究预测,尽管观察性研究显示血浆支链氨基酸(BCAAs)与2型糖尿病相关,但通过靶向BCAA分解代谢通路降低BCAA水平,不太可能降低2型糖尿病风险。借助大样本量和高质量基因型填充,研究发现19.4%的可信精细定位变异次等位基因频率在0.1%至1%之间,且这些变异在预测的错义变异和剪接改变变异中富集两倍。结果强调了将低频变异纳入遗传关联研究的价值。

为什么值得关注

编辑短评

该研究对近 62 万人的循环代谢性状开展遗传分析,构建大规模代谢 mQTL 图谱,识别一批新的代谢遗传位点;证实代谢性状受遗传调控、存在广泛多效性,通过共定位与孟德尔随机化证明部分代谢物是疾病的中间介导因子,为代谢相关疾病机制解析和药物靶点挖掘提供遗传证据。

查看扩展信息

完整作者

Ralf Tambets、Mihkel Jesse、Jaanika Kronberg、Adriaan van der Graaf、Erik Abner、Urmo Võsa、Ida Rahu、Nele Taba、Anastassia Kolde、Dzvenymyra Yarish、Sariyya Abdullayeva、Anastasiia Alekseienko、Andres Veidenberg、Estonian Biobank Research Team、Krista Fischer、Zoltán Kutalik、Tõnu Esko、Kaur Alasoo、Priit Palta

作者机构

  • Institute of Computer Science, University of Tartu, Tartu, Estonia.
  • Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia.
  • Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • University Center for Primary Care and Public Health, Unisanté, University of Lausanne, Lausanne, Switzerland.
  • Institute of Computer Science, University of Tartu, Tartu, Estonia. kaur.alasoo@ut.ee.
  • Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. priit.palta@ut.ee.

技术路线

Estonian Biobank与UK Biobank共619,372名个体的249项循环代谢特征 → GWAS荟萃分析

最近 5 个完整年度引用趋势

0110202102022020230202402025

不含 2026 年,仅展示最近 5 个完整年度。

数据来源:openalex更新时间:2026/11/02 01:41