Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAMasahiro Kanai, Juha Karjalainen, Georgia Panagiotaropoulou, Yuanxiang Zhang, Zhili Zheng, Mark J. Daly, Mary Pat Reeve, Mary Pat Reeve, Mitja Kurki, Wei Zhou, Aarno Palotie & Mark J. DalyCenter for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USAMasahiro Kanai, Georgia Panagiotaropoulou, Yuanxiang Zhang, Kosaku Nanki, Toshimi Yoshida, Kai Liu, Daniel B. Graham & Ramnik J. XavierDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA, USAMasahiro Kanai, Kosaku Nanki, Toshimi Yoshida, Kai Liu, Daniel B. Graham & Ramnik J. XavierInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, FinlandMasahiro Kanai, Rodosthenis S. Rodosthenous, Juha Karjalainen, Yuanxiang Zhang, Sanni Ruotsalainen, Zhili Zheng, Mark J. Daly, Rodosthenis S. Rodosthenous, Mary Pat Reeve, Mary Pat Reeve, Mitja Kurki, Wei Zhou, Aarno Palotie & Mark J. DalyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USAToni M. Delorey, Shane Murphy, Isabella Teixeira-Soldano, Hee Seung Hwang, Cristin McCabe, Eric Chen, Marla Glean, Nitya Mehrotra, Emily P. Finan, Daniel Chafamo, Yixiao Zhu, Caroline B. M. Porter, Orr Ashenberg & Ramnik J. XavierBlood Service Biobank, Finnish Red Cross Blood Service, Vantaa, FinlandJarno Honkanen, Julianna Juvila, Jussi Halonen, Kimmo Pitkänen & Jukka PartanenProgram in Infectious Disease and Microbiome, Broad Institute of MIT and Harvard, Cambridge, MA, USAGeorgia Panagiotaropoulou, Yuanxiang Zhang, Kosaku Nanki, Toshimi Yoshida, Kai Liu, Daniel B. Graham & Ramnik J. XavierAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USAGeorgia Panagiotaropoulou, Yuanxiang Zhang, Zhili Zheng, Mark J. Daly, Mitja Kurki & Mark J. DalyStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USAGeorgia Panagiotaropoulou, Yuanxiang Zhang, Zhili Zheng, Mark J. Daly, Mitja Kurki, Wei Zhou, Aarno Palotie & Mark J. DalyResearch and Development, Finnish Red Cross Blood Service, Helsinki, FinlandMikko Arvas & Jukka PartanenDepartment of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanYoshihiko Tomofuji, Daiki Tokuyasu, Shinichi Namba, Kyuto Sonehara & Yukinori OkadaLaboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanYoshihiko Tomofuji, Shinichi Namba, Kyuto Sonehara & Yukinori OkadaDepartment of Neurology, Keio University School of Medicine, Tokyo, JapanDaiki TokuyasuLaboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), The University of Osaka, Suita, JapanYukinori OkadaPremium Research Institute for Human Metaverse Medicine (WPI-PRIMe), The University of Osaka, Suita, JapanYukinori OkadaPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USAWei Zhou & Aarno PalotieGene Lay Institute of Immunology and Inflammation, Brigham and Women’s Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USARamnik J. XavierHuman Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, JapanKoichi Matsuda, Takayuki Morisaki, Natsuhiko Kumasaka & Akiko NagaiGraduate School of Frontier Sciences, The University of Tokyo, Tokyo, JapanKoichi Matsuda, Takayuki Morisaki & Akiko NagaiDepartment of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanNorihiro Harada & Sonoko HaradaAtopy (Allergy) Research Center, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanSonoko HaradaDepartment of Hematology, Nippon Medical School, Tokyo, JapanYasunobu Nagata, Satoshi Wakita & Hiroki YamaguchiAbbVie, Chicago, IL, USABridget Riley-Gillis, Howard Jacob, Jeffrey Waring, Bridget Riley-Gillis, Fedik Rahimov, Adam Ziemann, Nizar Smaoui, Anne Lehtonen, Apinya Lertratanakul, Relja Popovic, Mengzhen Liu, Anneke Den Hollander, Jan Freudenberg, Britney Milkovich, Andrew Blumenfeld & Tushar KumarAstraZeneca, Cambridge, UKCoralie Viollet, Slavé Petrovski, Ioanna Tachmazidou, Dirk Paul, Bram Prins, Eleanor Wheeler, Kousik Kundu, Santosh Atanur, Andrew Lowe, Thomas Spargo, Oliver Burren & Margarete FabreBayer, Leverkusen, GermanyAlix Berton, Santha Ramakrishnan, Fabio Baschiera, Hans van Leeuwen, Himanshu Manchanda, Karl Heilbron, Martin Rao, Nicole Schmidt, Samu Kurki, Johanna Mielke, Juho Immonen, Thomas Battram & Tobias HogrebeBiogen, Cambridge, MA, USAEllen Tsai, Susan Eaton, Ketian Yu, Stephanie Loomis & Coro Paisan-RuizBoehringer Ingelheim, Ingelheim am Rhein, GermanyZhihao Ding, Marc Jung, Hanati Tuoken, Elke Markert, Frank Li, Yao Hu, Christoph Ogris, Eric Simon, Julio Cesar Bolivar Lopez & Monika FryszBristol Myers Squibb, New York, NY, USAEmily Holzinger, Robert Plenge, Joseph Maranville, Shameek Biswas, Benjamin Sun, Marla Hochfeld, Cara Carty, Michael Turchin, Neelakshi Jog, Corneliu Bodea, Janie Shelton, Chen Li, Kritika Singh, Peng Jiang, Stephanie Loomis, Elena Sanchez, Lilith Moss, Zijie Zhao & Anna PodgornaiaGenentech, San Francisco, CA, USAMark McCarthy, Rion Pendergrass, Natalie Bowers, Edmond Teng, Tim Lu, Hubert Chen, Jennifer Schutzman, Erich Strauss, Hao Chen, David Choy, Brian Yaspan, Cameron Adams, Michael Rothenberg, Sergio Dellepiane, Anubha Mahajan, Michael Holmes, Diana Chang & Tushar BhangaleGlaxoSmithKline, Collegeville, PA, USAJonathan Davitte, Janet Kumar, Charli Harlow, Lea Sarow-Blat, Diana L. Cousminer, Jagtar Nijjar, Jessica Chao, Michal Magid, Shashank Jariwala, Chris Floyd, Dan Swerdlow, Erding Hu, Prerak Desai, Stephen Haddad, Damien Croteau-Chonka, Billy Fahy & Paola BronsonMerck, Kenilworth, NJ, USAChia-Yen Chen, Neha Raghavan, Jae-Hoon Sul, Jason Miller, Fabiana Farias, Andrey Loboda, Jorge Del-Aguila, Elisabeth Vollmann, Jozsef Karman, Julie Fiore, Rajesh Kamath, Andrei Popescu, Delphine Fagegaltier, Travis Barr, Aristide Merola, Oliver Freeman & Simonne LongerichPfizer, New York, NY, USAMelis Atalar Aksit, Anna Vlahiotis, Xinli Hu, Kirsi Kalpala, Melissa Miller, Nan Bing, Jaakko Parkkinen, Heli Lehtonen, Stefan McDonough, Ying Wu, Erin Macdonald-Dunlop, Jessica Chung, Michael McLean, Joshua Chiou, Hye In Kim, Sivakumar Pitchumani, Sumedha Jassal & Madhurima SaxenaTranslational Sciences, Sanofi R&D, Framingham, MA, USAKatherine Klinger, Clement Chatelain, Jorg Blankenstein, Catherine O’Riordan, Samuel Lessard, Suzanne Jacobs, Hamid Mattoo, David Habiel & Guanling HuanMaze Therapeutics, San Francisco, CA, USAKarol Estrada, Robert Graham, Sahar Mozaffari & Christopher DeBoeverJohnson & Johnson Innovative Medicine, Spring House, PA, USADawn Waterworth, Karen He, Ekaterina Khramtsova, Amy Hart, Meijian Guan, Alessandro Porello, P. Dunnmon, Sara Gale, Brice Keyes, John Kwon, Jonathan Sherlock, Matt Loza, Chris Whelan, W. Galpern, Yanfei Zhang, Mona Selej & Abolfazl Doostparast TorshiziNovartis Institutes for BioMedical Research, Cambridge, MA, USAChris O’Donnell, Nicole Renaud, Ma’en Obeidat, Jonathan Chung, Jonas Zierer, Mari Niemi, Enrico Ferrero, Nikos Patsopoulos, Nancy Finkel, Sabina Pfister, Shola Richards, Katherine McCauley, Xiaobo Xia & Mike MendelsonHiLIFE, University of Helsinki, Helsinki, FinlandTomi P. MäkeläInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, FinlandJaakko Kaprio, Samuli Ripatti, Felix Vaura, Nina Mars, Esa Pitkänen, Hannele Laivuori, Katja Kivinen, Elisabeth Widen, Taru Tukiainen, Hanna Ollila, Elmo Saarentaus, Anne Kerola, Eero Vuoksimaa, Joni Lindbohm, Zhiyu Yang, Matthew Sampson, Adrian Banerji, Michelle McNulty, Aoxing Liu, Joel Rämö, Austin Argentieri, Amanda Elliott, Anu Jalanko, Risto Kajanne, Mervi Aavikko, Helen Cooper, Denise Öller, Tarja Laitinen, Auli Toivola, Pietro Della Briotta Parolo, Arto Lehisto, Juha Mehtonen, Reza Jabal, Mutaamba Maasha, Samuel Jones, Raymond Walters, Paavo Häppölä, L. Elisa Lahtela, Johanna Paltta, Juulia Partanen, Mari Kaunisto, Elina Kilpeläinen, Tianduanyi Wang, Timo P. Sipilä, Oluwaseun Alexander Dada, Awaisa Ghazal, Rigbe Weldatsadik, Jaska Uimonen, Kati Donner, Susanna Lemmelä, Shanmukha Sampath Padmanabhuni, Marika Kaakinen, Shuang Luo, Vincent Llorens, Dawit Yohannes & Iina LaakArctic Biobank, Oulu, FinlandMinna RuddockUniversity of Oulu, Oulu, FinlandMinna Ruddock, Teija Kekonen, Raisa Serpi, Reetta Hinttala, Johannes Kettunen, Heidi Silven, Eeva Sliz, Riikka Arffman, Susanna Savukoski, Riitta Kaarteenaho & Jaakko TyrmiAuria Biobank, Turku, FinlandLila Kallio, Antti Hakanen & Johanna SchleutkerUniversity of Turku, Turku, FinlandLila Kallio, Antti Hakanen, Johanna Schleutker, Laura Kuusalo, Laura Pirilä, Tapio Hellman, Matti Vuori, Teemu Niiranen & Johanna PalttaWellbeing Services County of Southwest Finland, Turku, FinlandLila Kallio, Antti Hakanen, Johanna Schleutker, Laura Pirilä, Juha Rinne, Roosa Kallionpää, Markku Voutilainen, Antti Palomäki, Riitta Lahesmaa, Kaj Metsärinne, Jenni Aittokallio, Klaus Elenius, Sirkku Peltonen, Leena Koulu, Ulvi Gursoy, Varpu Jokimaa & Tytti WillbergTHL Biobank, Helsinki, FinlandTerhi Kilpi, Markus Perola, Tiina Wahlfors, Päivi Laiho, Teemu Paajanen, Arto Pietilä & Aki HavulinnaFinnish Institute for Health and Welfare (THL), Helsinki, FinlandTerhi Kilpi, Markus Perola, Tiina Wahlfors, Veikko Salomaa, Jaana Suvisaari, Teemu Niiranen, Päivi Laiho, Teemu Paajanen, Arto Pietilä & Aki HavulinnaHelsinki Biobank, Helsinki, FinlandTaneli Raivio, Eero Punkka, Olli Carpén & Anu LoukolaHelsinki University and Hospital District of Helsinki and Uusimaa, Helsinki, FinlandTaneli Raivio, Eero Punkka, Olli Carpén & Anu LoukolaNorthern Finland Biobank Borealis, Oulu, FinlandTeija Kekonen, Raisa Serpi, Reetta Hinttala & Johannes KettunenWellbeing Services County of North Ostrobothnia, Oulu, FinlandTeija Kekonen, Raisa Serpi, Reetta Hinttala, Johannes Kettunen, Timo Blomster, Johanna Huhtakangas, Terttu Harju, Kaisa Tasanen, Laura Huilaja, Vuokko Anttonen, Marja Vääräsmäki, Outi Uimari, Laure Morin-Papunen, Maarit Niinimäki & Terhi PiltonenFinnish Clinical Biobank Tampere, Tampere, FinlandKati Kristiansson, Sanna Siltanen & Mika KähönenUniversity of Tampere, Tampere, FinlandKati Kristiansson, Sanna Siltanen, Mika Kähönen, Jaakko Tyrmi, Harri Siirtola & Javier Gracia-TabuencaWellbeing Services County of Pirkanmaa, Tampere, FinlandKati Kristiansson, Sanna Siltanen, Mika Kähönen, Jukka Peltola, Airi Jussila, Katri Kaukinen, Pia Isomäki, Jussi Hernesniemi, Annika Auranen, Hannu Uusitalo, Teea Salmi, Venla Kurra, Laura Kotaniemi-Talonen & Argyro Bizaki-VallaskangasBiobank of Eastern Finland, Kuopio, FinlandVeli-Matti Kosma, Arto Mannermaa & Hanna KujalaUniversity of Eastern Finland, Kuopio, FinlandVeli-Matti Kosma, Arto Mannermaa, Hanna Kujala, Pirkko Pussinen, Mikko Hiltunen & Eino SoljeWellbeing Services County of North Savo, Kuopio, FinlandVeli-Matti Kosma, Arto Mannermaa, Hanna Kujala, Valtteri Julkunen, Reetta Kälviäinen, Hilkka Soininen, Mikko Kiviniemi, Oili Kaipiainen-Seppänen, Margit Pelkonen, Päivi Auvinen, Maria Siponen, Liisa Suominen, Päivi Mäntylä & Kai KaarnirantaCentral Finland Biobank, Jyväskylä, FinlandJari Laukkanen & Tiina JokelaUniversity of Jyväskylä, Jyväskylä, FinlandJari Laukkanen, Tiina Jokela & Eija LaakkonenWellbeing Services County of Central Finland, Jyväskylä, FinlandJari Laukkanen & Tiina JokelaFinnish Biobank Cooperative—FINBB, Turku, FinlandMervi Ahlroth, Johanna Mäkelä, Johanna Mäkelä, Pauli Wihuri, Tom Southerington & Meri LähteenmäkiBusiness Finland, Helsinki, FinlandOuti TuovilaFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandKatriina Aalto-SetäläEstonian Biobank, Tartu, EstoniaTriin Laisk & Natalia PujolFinnish Red Cross Blood Service, Helsinki, FinlandSatu Koskela & Jouni LauronenFinnish Hematology Registry and Clinical Biobank, Helsinki, FinlandSatu Koskela & Jouni LauronenHelsinki University Central Hospital, Helsinki, FinlandKristiina AittomäkiHelsinki University Hospital and University of Helsinki, Helsinki, FinlandPirkko Pussinen, Tuomo Meretoja, Heikki Joensuu, Peeter Karihtala, Emma Juuri, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Fredrik Åberg, Daniel Gordin, Patrik Finne, Joni A. Turunen & Sanna Toppila-SalmiHospital District of Helsinki and Uusimaa, Helsinki, FinlandDaniel Gordin, Minna Raivio, Pentti Tienari, Martti Färkkilä, Jukka Koskela, Sampsa Pikkarainen, Kari Eklund, Paula Kauppi, Juha Sinisalo, Marja-Riitta Taskinen, Tiinamaija Tuomi, Timo Hiltunen, Johanna Mattson, Eveliina Salminen, Terhi Ollila, Katariina Hannula-Jouppi, Oskari Heikinheimo, Ilkka Kalliala, Lauri Aaltonen, Erkki Isometsä, Antti Aarnisalo, Ilkka Immonen, Salla Ranta & Filip ScheperjansFolkhälsan Research Center, Helsinki, FinlandJoni A. TurunenHarvard Medical School, Boston, MA, USAMatthew Sampson, Adrian Banerji & Michelle McNultyBroad Institute, Cambridge, MA, USAMatthew Sampson, Adrian Banerji, Michelle McNulty, Aoxing Liu, Joel Rämö, Austin Argentieri, Amanda Elliott, Reza Jabal, Mutaamba Maasha & Raymond WaltersMassachusetts General Hospital, Boston, MA, USAAmanda ElliottNorthern Ostrobothnia Hospital District, Oulu, FinlandElisa RahikkalaOulu University Hospital and University of Oulu, Oulu, FinlandKirsi SipiläUniversity of Eastern Finland and Kuopio University Hospital, Kuopio, FinlandValtteri Julkunen, Ville Leinonen & Sanna Toppila-SalmiUniversity of Gothenburg, Gothenburg, SwedenHannu KankaanrantaSeinäjoki Central Hospital, Seinäjoki, FinlandHannu KankaanrantaTampere University, Tampere, FinlandHannu KankaanrantaUniversity of Helsinki and Helsinki University Hospital, Helsinki, FinlandAntti MäkitieUniversity of Helsinki, Helsinki, FinlandIiris Hovatta, Niko Välimäki, Minttu Marttila, Anne Portaankorva & Sofia KuitunenUniversity of Lodz, Lodz, PolandKai KaarnirantaGlaxoSmithKline, Brentford, UKFanli Xu, Laura Addis, John Eicher, Linda McCarthy, Jorge Esparza Gordillo, Joanna Betts, Rajashree Mishra, Audrey Chu & Diptee KulkarniGlaxoSmithKline, Espoo, FinlandKirsi AuroGlaxoSmithKline, Stevenage, UKDavid PulfordJanssen-Cilag Oy, Espoo, FinlandSauli VuotiJohnson & Johnson Innovative Medicine, Boston, MA, USADermot ReillyJohnson & Johnson Innovative Medicine, Titusville, NJ, USAQingqin S. LiNovartis, Basel, SwitzerlandMajd Mouded & Debby NgoM. Kanai, A.P., D.B.G., M.J.D. and R.J.X. conceived and designed the study. J. Honkanen, R.S.R., J.J., J. Halonen, M.A., K.P. and J.P. coordinated sample collection at the Finnish Red Cross Blood Service. T.M.D., S.M., I.T.-S., C.M., K.N., T.Y., K.L., M.G., N.M. and E.P.F. performed single-cell experiments. M. Kanai, H.S.H., E.C., D.C., Y. Zhu and C.B.M.P. processed multiome data. M. Kanai, R.S.R., J.K., G.P., Y. Zhang, S.R., Z.Z., M.P.R., M. Kurki, O.A. and W.Z. performed statistical analyses. M. Kanai developed the CASCADE framework, software and interactive browser. M. Kanai, Y.T., D.T., S.N., K.S. and Y.O. performed the BioBank Japan replication analyses. M.J.D. and R.J.X. jointly supervised the study. M. Kanai, D.B.G., M.J.D. and R.J.X. wrote the manuscript. All of the authors read, revised and approved the final manuscript.
