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全世界の5つの集団から746,667人のトランス民族および祖先特有の血液細胞遺伝学

Ming-Huei Chen ¹, Laura M Raffield ², Abdou Mousas ³

¹The Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA 01702, USA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA 01702, USA.
²Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
³Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
⁴Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
⁵Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
⁶The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁷Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
⁸BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
⁹BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; MRC Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, UK; Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge CB2 0QQ, UK.
¹⁰Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK.
¹¹Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02446, USA.
¹²Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
¹³Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
¹⁴Département de Pharmacologie et Physiologie, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
¹⁵Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
¹⁶Department of Statistics and Operation Research, University of North Carolina, Chapel Hill, NC 27599, USA.
¹⁷Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8581, Japan.
¹⁸Department of Biostatistics, University of Washington, Seattle, WA 98101, USA.
¹⁹Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK.
²⁰Translational Health Sciences, Musculoskeletal Research Unit, Bristol Medical School, University of Bristol, Bristol BS10 5NB, UK.
²¹Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
²²The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Hasso-Plattner-Institut, Universität Potsdam, Potsdam 14469, Germany.
²³Department of Medicine, University of Washington, Seattle, WA 98101, USA.
²⁴Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam 3015, the Netherlands.
²⁵Laboratory of Epidemiology and Population Science, National Institute on Aging/NIH, Baltimore, MD 21224, USA.
²⁶Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA; Department of Medicine, Division on Aging, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
²⁷Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.
²⁸Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
²⁹BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge CB2 0QQ, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge CB10 1SA, UK; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge CB2 0QQ, UK; British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
³⁰BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge CB2 0QQ, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge CB10 1SA, UK; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge CB2 0QQ, UK; British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
³¹Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon 69008, France; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.
³²Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
³³Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK; Imperial Biomedical Research Centre, Imperial College London and Imperial College NHS Healthcare Trust, London SW7 2AZ, UK; Medical Research Council-Public Health England Centre for Environment, Imperial College London, London SW7 2AZ, UK; UK Dementia Research Institute, Imperial College London, London SW7 2AZ, UK; Health Data Research UK - London, London SW7 2AZ, UK.
³⁴Broad Institute of Harvard and MIT, Cambridge, MA 02446, USA.
³⁵Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Epidemiology, University of Washington, Seattle, WA 98101, USA.
³⁶Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015, the Netherlands.
³⁷Broad Institute of Harvard and MIT, Cambridge, MA 02446, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.
³⁸Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
³⁹Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁴⁰BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Novo Nordisk Research Centre Oxford, Innovation Building, Old Road Campus, Oxford OX3 7FZ, UK.
⁴¹Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai 201203, China.
⁴²Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany; Chair of Experimental Bioinformatics, Research Group Computational Systems Medicine, Technical University of Munich, Freising-Weihenstephan 85354, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald 17475, Germany.
⁴³Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland; Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland.
⁴⁴Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan.
⁴⁵Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
⁴⁶Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.
⁴⁷Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
⁴⁸Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland.
⁴⁹Department of Internal Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
⁵⁰Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg 2000, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
⁵¹Duke Molecular Physiology Institute, Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC 27701, USA.
⁵²Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.
⁵³Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan.
⁵⁴Division of Molecular Pathology, The Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan.
⁵⁵German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald 17475, Germany; Institue of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
⁵⁶Department of Cardiology, Heart Center, Tampere University Hospital, Tampere 33521, Finland; Department of Cardiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33014, Finland.
⁵⁷Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK; British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Department of Hematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
⁵⁸Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
⁵⁹Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Epidemiology, University of Washington, Seattle, WA 98101, USA; Department of Health Services, University of Washington, Seattle, WA 98101, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA 98101, USA.
⁶⁰Centre for Population Health Research, University of Turku and Turku University Hospital, Turku 20521, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20521, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland.
⁶¹The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge CB2 0QQ, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; Department of Haematology, Churchill Hospital, Oxford OX3 7LE, UK; NHS Blood and Transplant - Oxford Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
⁶²Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA.
⁶³The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
⁶⁴Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA 01002, USA.
⁶⁵BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Rutherford Fund Fellow, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
⁶⁶Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶⁷Montreal Heart Institute, Montreal, QC H1T 1C8, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
⁶⁸School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 1UL, UK.
⁶⁹Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam 3015, the Netherlands; Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.
⁷⁰Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald 17475, Germany.
⁷¹German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald 17475, Germany; Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
⁷²National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
⁷³Atlanta VA Medical Center, Decatur, GA 30033, USA.
⁷⁴Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
⁷⁵BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge CB2 0QQ, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge CB10 1SA, UK.
⁷⁶Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA; Quantitative and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
⁷⁷Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
⁷⁸MRC Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge CB2 0QQ, UK; NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Strangeways Laboratory, Cambridge CB1 8RN, UK.
⁷⁹Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece; Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.
⁸⁰Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Laboratory of Statistical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
⁸¹Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK; Department of Hematology, University of Cambridge, Cambridge CB2 0PT, UK.
⁸²Department of Epidemiology, University of Washington, Seattle, WA 98109, USA.

⁰The Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA 01702, USA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA 01702, USA.

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2020年9月5日

PubMedで要約を見る

まとめ

この研究は,血液の特徴に関する新しい遺伝的関連性を明らかにし,分析に多種多様なグローバル人口を含んでいます. 非ヨーロッパ人の祖先を組み込むことは,血液学的な現象型に影響を与える遺伝的変異の発見を高めます.

科学分野

遺伝学
人口遺伝学
ゲノミクス

背景

ゲノム・ワイド・アソシエーション・スタディ (GWAS) は,主にヨーロッパの祖先集団における遺伝的位置を特定しています.
これは多様なヒト集団における多くの特徴の遺伝的構造の理解を制限している.
より幅広い遺伝的多様性を捉えるにはより包括的なアプローチが必要である.

研究の目的

跨民族的なメタ解析を行うことにより,血液学的特性の新しい特質変異関連性を特定する.
非ヨーロッパ人集団における祖先特有の変種とその機能的影響を調査する.
異なる祖先の血型に関する遺伝的構造と進化的圧力を比較する.

主な方法

非ヨーロッパ人184,535人を含む746,000人を超える参加者の15の血液学的特徴のトランス民族的なメタ分析を行った.
祖先特有のメタ分析を行い, 代表が不足した集団における新しい変異を特定した.
機能的な変異を優先し,信頼性の高いセットサイズにトランス民族データの影響を評価するために,細かいマッピング技術を使用しました.

主要な成果

5552の特質変異関連が特定され,その中には以前ヨーロッパ人群で発見されなかった71の新規関連が含まれています.
リンパ球数に関連した南アジア人のIL7変種など,非ヨーロッパの祖先特有の分析で28の新規変種が発見されました.
民族間の精細なマッピングは,ヨーロッパだけの分析と比較して,信頼性の高いセットサイズを30%減少させました.

結論

トランス民族的なメタ解析は,血液学的特徴の遺伝的関連の発見を大幅に増加させます.
ヒトの遺伝的多様性とその健康への影響を総合的に理解するためには多様な世界の人口を含むことが不可欠です
これらの発見は,より広い範囲の生物学的洞察を明らかにするために,遺伝学の研究におけるグローバルな代表性の重要性を強調しています.

キーワード:

interleukin-7, 遺伝子構造, 精細マッピング, 選択的なスウィップ, 多遺伝的特徴スコア, 現象全体の関連性研究

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