Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease

Wei Zhou; Masahiro Kanai; Kuan-Han H Wu; Humaira Rasheed; Kristin Tsuo; Jibril B Hirbo; Ying Wang; Arjun Bhattacharya; Huiling Zhao; Shinichi Namba; Ida Surakka; Brooke N Wolford; Valeria Lo Faro; Esteban A Lopera-Maya; Kristi Läll; Marie-Julie Favé; Juulia J Partanen; Sinéad B Chapman; Juha Karjalainen; Mitja Kurki; Mutaamba Maasha; Ben M Brumpton; Sameer Chavan; Tzu-Ting Chen; Michelle Daya; Yi Ding; Yen-Chen A Feng; Lindsay A Guare; Christopher R Gignoux; Sarah E Graham; Whitney E Hornsby; Nathan Ingold; Said I Ismail; Ruth Johnson; Triin Laisk; Kuang Lin; Jun Lv; Iona Y Millwood; Sonia Moreno-Grau; Kisung Nam; Priit Palta; Anita Pandit; Michael H Preuss; Chadi Saad; Shefali Setia-Verma; Unnur Thorsteinsdottir; Jasmina Uzunovic; Anurag Verma; Matthew Zawistowski; Xue Zhong; Nahla Afifi; Kawthar M Al-Dabhani; Asma Al Thani; Yuki Bradford; Archie Campbell; Kristy Crooks; Geertruida H de Bock; Scott M Damrauer; Nicholas J Douville; Sarah Finer; Lars G Fritsche; Eleni Fthenou; Gilberto Gonzalez-Arroyo; Christopher J Griffiths; Yu Guo; Karen A Hunt; Alexander Ioannidis; Nomdo M Jansonius; Takahiro Konuma; Ming Ta Michael Lee; Arturo Lopez-Pineda; Yuta Matsuda; Riccardo E Marioni; Babak Moatamed; Marco A Nava-Aguilar; Kensuke Numakura; Snehal Patil; Nicholas Rafaels; Anne Richmond; Agustin Rojas-Muñoz; Jonathan A Shortt; Peter Straub; Ran Tao; Brett Vanderwerff; Manvi Vernekar; Yogasudha Veturi; Kathleen C Barnes; Marike Boezen; Zhengming Chen; Chia-Yen Chen; Judy Cho; George Davey Smith; Hilary K Finucane; Lude Franke; Eric R Gamazon; Andrea Ganna; Tom R Gaunt; Tian Ge; Hailiang Huang; Jennifer Huffman; Nicholas Katsanis; Jukka T Koskela; Clara Lajonchere; Matthew H Law; Liming Li; Cecilia M Lindgren; Ruth J F Loos; Stuart MacGregor; Koichi Matsuda; Catherine M Olsen; David J Porteous; Jordan A Shavit; Harold Snieder; Tomohiro Takano; Richard C Trembath; Judith M Vonk; David C Whiteman; Stephen J Wicks; Cisca Wijmenga; John Wright; Jie Zheng; Xiang Zhou; Philip Awadalla; Michael Boehnke; Carlos D Bustamante; Nancy J Cox; Segun Fatumo; Daniel H Geschwind; Caroline Hayward; Kristian Hveem; Eimear E Kenny; Seunggeun Lee; Yen-Feng Lin; Hamdi Mbarek; Reedik Mägi; Hilary C Martin; Sarah E Medland; Yukinori Okada; Aarno V Palotie; Bogdan Pasaniuc; Daniel J Rader; Marylyn D Ritchie; Serena Sanna; Jordan W Smoller; Kari Stefansson; David A van Heel; Robin G Walters; Sebastian Zöllner; Biobank of the Americas; Biobank Japan Project; BioMe; BioVU; CanPath - Ontario Health Study; China Kadoorie Biobank Collaborative Group; Colorado Center for Personalized Medicine; deCODE Genetics; Estonian Biobank; FinnGen; Generation Scotland; Genes & Health Research Team; LifeLines; Mass General Brigham Biobank; Michigan Genomics Initiative; National Biobank of Korea; Penn Medicine BioBank; Qatar Biobank; QSkin Sun and Health Study; Taiwan Biobank; HUNT Study; UCLA ATLAS Community Health Initiative; Uganda Genome Resource; UK Biobank; Alicia R Martin; Cristen J Willer; Mark J Daly; Benjamin M Neale

doi:10.1016/j.xgen.2022.100192

Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease

Cell Genom. 2022 Oct 12;2(10):100192. doi: 10.1016/j.xgen.2022.100192.

Authors

Wei Zhou^{1

2

3}, Masahiro Kanai^{1

2

3

4

5}, Kuan-Han H Wu⁶, Humaira Rasheed^{7

8

9}, Kristin Tsuo^{1

2

3}, Jibril B Hirbo^{10

11}, Ying Wang^{1

2

3}, Arjun Bhattacharya¹², Huiling Zhao⁹, Shinichi Namba⁵, Ida Surakka¹³, Brooke N Wolford^{6

7}, Valeria Lo Faro^{14

15

16}, Esteban A Lopera-Maya¹⁷, Kristi Läll¹⁸, Marie-Julie Favé¹⁹, Juulia J Partanen²⁰, Sinéad B Chapman^{2

3}, Juha Karjalainen^{1

2

3

20}, Mitja Kurki^{1

2

3

20}, Mutaamba Maasha^{1

2

3

20}, Ben M Brumpton^{7

21

22}, Sameer Chavan²³, Tzu-Ting Chen²⁴, Michelle Daya²³, Yi Ding^{12

25}, Yen-Chen A Feng²⁶, Lindsay A Guare²⁷, Christopher R Gignoux²³, Sarah E Graham¹³, Whitney E Hornsby¹³, Nathan Ingold^{28

29}, Said I Ismail³⁰, Ruth Johnson^{31

12}, Triin Laisk¹⁸, Kuang Lin³², Jun Lv³³, Iona Y Millwood^{32

34}, Sonia Moreno-Grau³⁵, Kisung Nam³⁶, Priit Palta^{18

20}, Anita Pandit³⁷, Michael H Preuss³⁸, Chadi Saad³⁰, Shefali Setia-Verma³⁹, Unnur Thorsteinsdottir⁴⁰, Jasmina Uzunovic¹⁹, Anurag Verma^{41

42}, Matthew Zawistowski³⁷, Xue Zhong^{10

11}, Nahla Afifi⁴³, Kawthar M Al-Dabhani⁴³, Asma Al Thani⁴³, Yuki Bradford²⁷, Archie Campbell⁴⁴, Kristy Crooks²³, Geertruida H de Bock⁴⁵, Scott M Damrauer^{27

42

46}, Nicholas J Douville^{47

48}, Sarah Finer⁴⁹, Lars G Fritsche³⁷, Eleni Fthenou⁴³, Gilberto Gonzalez-Arroyo^{35

50}, Christopher J Griffiths⁴⁹, Yu Guo⁵¹, Karen A Hunt⁵², Alexander Ioannidis^{35

53}, Nomdo M Jansonius¹⁴, Takahiro Konuma^{5

54}, Ming Ta Michael Lee³⁵, Arturo Lopez-Pineda^{35

50}, Yuta Matsuda⁵⁵, Riccardo E Marioni⁴⁴, Babak Moatamed³⁵, Marco A Nava-Aguilar^{35

50}, Kensuke Numakura⁵⁵, Snehal Patil³⁷, Nicholas Rafaels²³, Anne Richmond⁵⁶, Agustin Rojas-Muñoz³⁵, Jonathan A Shortt²³, Peter Straub^{10

11}, Ran Tao^{11

57}, Brett Vanderwerff³⁷, Manvi Vernekar⁵⁵, Yogasudha Veturi²⁷, Kathleen C Barnes²³, Marike Boezen⁴⁵, Zhengming Chen^{32

34}, Chia-Yen Chen⁵⁸, Judy Cho³⁸, George Davey Smith^{9

59}, Hilary K Finucane^{1

2

3}, Lude Franke¹⁷, Eric R Gamazon^{10

11

60}, Andrea Ganna^{1

2

20}, Tom R Gaunt^{9

59}, Tian Ge^{61

62}, Hailiang Huang^{1

2}, Jennifer Huffman⁶³, Nicholas Katsanis³⁵, Jukka T Koskela²⁰, Clara Lajonchere^{64

65}, Matthew H Law^{28

29}, Liming Li³³, Cecilia M Lindgren⁶⁶, Ruth J F Loos^{38

67}, Stuart MacGregor²⁸, Koichi Matsuda⁶⁸, Catherine M Olsen²⁸, David J Porteous⁴⁴, Jordan A Shavit^{69

70}, Harold Snieder⁴⁵, Tomohiro Takano⁵⁵, Richard C Trembath⁷¹, Judith M Vonk⁴⁵, David C Whiteman²⁸, Stephen J Wicks²³, Cisca Wijmenga¹⁷, John Wright⁷², Jie Zheng⁹, Xiang Zhou³⁷, Philip Awadalla^{19

73}, Michael Boehnke³⁷, Carlos D Bustamante^{35

53

74}, Nancy J Cox^{10

11}, Segun Fatumo^{75

76

77}, Daniel H Geschwind^{64

78

79}, Caroline Hayward⁵⁶, Kristian Hveem^{7

21}, Eimear E Kenny⁸⁰, Seunggeun Lee³⁶, Yen-Feng Lin^{24

81

82}, Hamdi Mbarek³⁰, Reedik Mägi¹⁸, Hilary C Martin⁸³, Sarah E Medland²⁸, Yukinori Okada^{5

84

85

86

87}, Aarno V Palotie^{1

2

20}, Bogdan Pasaniuc^{12

25

64

78

88}, Daniel J Rader^{27

41}, Marylyn D Ritchie²⁷, Serena Sanna^{17

89}, Jordan W Smoller^{61

62}, Kari Stefansson⁴⁰, David A van Heel⁵², Robin G Walters^{32

34}, Sebastian Zöllner³⁷; Biobank of the Americas; Biobank Japan Project; BioMe; BioVU; CanPath - Ontario Health Study; China Kadoorie Biobank Collaborative Group; Colorado Center for Personalized Medicine; deCODE Genetics; Estonian Biobank; FinnGen; Generation Scotland; Genes & Health Research Team; LifeLines; Mass General Brigham Biobank; Michigan Genomics Initiative; National Biobank of Korea; Penn Medicine BioBank; Qatar Biobank; QSkin Sun and Health Study; Taiwan Biobank; HUNT Study; UCLA ATLAS Community Health Initiative; Uganda Genome Resource; UK Biobank; Alicia R Martin^{1

2

3}, Cristen J Willer^{6

13

70}, Mark J Daly^{1

2

3

20}, Benjamin M Neale^{1

2

3}

Affiliations

¹ Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
² Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
⁵ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
⁶ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
⁷ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
⁸ Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway.
⁹ MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Bristol, UK.
¹⁰ Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹¹ Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
¹² Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹³ Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
¹⁴ University of Groningen, UMCG, Department of Ophthalmology, Groningen, the Netherlands.
¹⁵ Department of Clinical Genetics, Amsterdam University Medical Center (AMC), Amsterdam, the Netherlands.
¹⁶ Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹⁷ University of Groningen, UMCG, Department of Genetics, Groningen, the Netherlands.
¹⁸ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
¹⁹ Ontario Institute for Cancer Research, Toronto, ON, Canada.
²⁰ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
²¹ HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
²² Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
²³ University of Colorado - Anschutz Medical Campus, Aurora, CO, USA.
²⁴ Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
²⁵ Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA.
²⁶ Division of Biostatistics, Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
²⁷ Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁸ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
²⁹ Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
³⁰ Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.
³¹ Department of Computer Science, University of California, Los Angeles, Los Angeles, CA, USA.
³² Nuffield Department of Population Health, University of Oxford, Oxford, UK.
³³ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
³⁴ MRC Population Health Research Unit, University of Oxford, Oxford, UK.
³⁵ Galatea Bio, Inc., Hialeah, FL, USA.
³⁶ Graduate School of Data Science, Seoul National University, Seoul, South Korea.
³⁷ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
³⁸ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³⁹ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴⁰ deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
⁴¹ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴² Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA.
⁴³ Qatar Biobank for Medical Research, Qatar Foundation for Education, Science, and Community, Doha, Qatar.
⁴⁴ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
⁴⁵ Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands.
⁴⁶ Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴⁷ Department of Anesthesiology, Michigan Medicine, Ann Arbor, MI, USA.
⁴⁸ Institute of Healthcare Policy & Innovation, University of Michigan, Ann Arbor, MI, USA.
⁴⁹ Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
⁵⁰ Amphora Health, Morelia, Michoacan, Mexico.
⁵¹ Chinese Academy of Medical Sciences, Beijing, China.
⁵² Blizard Institute, Queen Mary University of London, London, UK.
⁵³ Stanford University School of Medicine, Stanford, CA, USA.
⁵⁴ Central Pharmaceutical Research Institute, Japan Tobacco, Inc., Takatsuki 569-1125, Japan.
⁵⁵ Genomelink, Inc., Berkeley, CA, USA.
⁵⁶ Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
⁵⁷ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁸ Biogen, Cambridge, MA, USA.
⁵⁹ NIHR Bristol Biomedical Research Centre, Bristol, UK.
⁶⁰ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
⁶¹ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶² Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
⁶³ Centre for Population Genomics, VA Boston Healthcare System, Boston, MA, USA.
⁶⁴ Institute of Precision Health, University of California, Los Angeles, Los Angeles, CA, USA.
⁶⁵ Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁶⁶ Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
⁶⁷ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
⁶⁸ Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
⁶⁹ University of Michigan, Department of Pediatrics, Ann Arbor, MI 48109, USA.
⁷⁰ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
⁷¹ School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
⁷² Bradford Institute for Health Research, Bradford Teaching Hospitals National Health Service (NHS) Foundation Trust, Bradford, UK.
⁷³ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁷⁴ Chan Zuckerberg Biohub, San Francisco, CA, USA.
⁷⁵ The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM, Entebbe, Uganda.
⁷⁶ London School of Hygiene & Tropical Medicine, London, UK.
⁷⁷ Medical Research Council/Uganda Virus Research Institute/London School of Hygiene and Tropical Medicine (MRC/UVRI/LSHTM) Uganda Research Unit, Entebbe, Uganda.
⁷⁸ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁷⁹ Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁸⁰ Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸¹ Department of Public Health & Medical Humanities, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁸² Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁸³ Human Genetics Programme, Wellcome Sanger Institute, Hinxton, UK.
⁸⁴ Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
⁸⁵ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita 565-0871, Japan.
⁸⁶ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁸⁷ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita 565-0871, Japan.
⁸⁸ Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁸⁹ Institute for Genetics and Biomedical Research (IRGB), National Research Council (CNR), Cagliari, Italy.

Abstract

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.

Keywords: GWAS; ancestry diversity; biobank; genetic association studies; meta-analysis; phenotype harmonization.

Abstract

Grants and funding