FinnGen provides genetic insights from a well-phenotyped isolated population

doi:10.1038/s41586-022-05473-8

. 2023 Jan;613(7944):508-518.

doi: 10.1038/s41586-022-05473-8. Epub 2023 Jan 18.

FinnGen provides genetic insights from a well-phenotyped isolated population

Mitja I Kurki^{1

2

3

4}, Juha Karjalainen^{1

2

3

4}, Priit Palta^{1

5}, Timo P Sipilä¹, Kati Kristiansson⁶, Kati M Donner¹, Mary P Reeve¹, Hannele Laivuori^{1

7

8

9}, Mervi Aavikko¹, Mari A Kaunisto¹, Anu Loukola¹⁰, Elisa Lahtela¹, Hannele Mattsson⁶, Päivi Laiho⁶, Pietro Della Briotta Parolo¹, Arto A Lehisto¹, Masahiro Kanai^{1

2

3

4

11}, Nina Mars¹, Joel Rämö¹, Tuomo Kiiskinen¹, Henrike O Heyne^{1

2

3

12

13}, Kumar Veerapen^{1

2

3

4}, Sina Rüeger¹, Susanna Lemmelä^{1

6}, Wei Zhou^{2

3

4}, Sanni Ruotsalainen¹, Kalle Pärn¹, Tero Hiekkalinna⁶, Sami Koskelainen⁶, Teemu Paajanen⁶, Vincent Llorens¹, Javier Gracia-Tabuenca¹⁴, Harri Siirtola¹⁴, Kadri Reis⁵, Abdelrahman G Elnahas⁵, Benjamin Sun^{15

16}, Christopher N Foley^{17

18}, Katriina Aalto-Setälä¹⁹, Kaur Alasoo²⁰, Mikko Arvas²¹, Kirsi Auro²², Shameek Biswas²³, Argyro Bizaki-Vallaskangas²⁴, Olli Carpen¹⁰, Chia-Yen Chen²⁵, Oluwaseun A Dada¹, Zhihao Ding²⁶, Margaret G Ehm²⁷, Kari Eklund^{28

29}, Martti Färkkilä³⁰, Hilary Finucane^{2

3

4}, Andrea Ganna^{1

2

3

4}, Awaisa Ghazal¹, Robert R Graham³¹, Eric M Green³¹, Antti Hakanen³², Marco Hautalahti³³, Åsa K Hedman^{34

35}, Mikko Hiltunen³⁶, Reetta Hinttala^{37

38

39}, Iiris Hovatta^{40

41}, Xinli Hu³⁴, Adriana Huertas-Vazquez⁴², Laura Huilaja^{43

44}, Julie Hunkapiller⁴⁵, Howard Jacob⁴⁶, Jan-Nygaard Jensen²⁶, Heikki Joensuu⁴⁷, Sally John²⁵, Valtteri Julkunen^{48

49}, Marc Jung²⁶, Juhani Junttila⁵⁰, Kai Kaarniranta^{51

52}, Mika Kähönen^{19

53}, Risto Kajanne¹, Lila Kallio³², Reetta Kälviäinen^{54

55}, Jaakko Kaprio^{1

56}; FinnGen; Nurlan Kerimov²⁰, Johannes Kettunen^{6

38

57}, Elina Kilpeläinen¹, Terhi Kilpi⁶, Katherine Klinger⁵⁸, Veli-Matti Kosma^{59

60}, Teijo Kuopio⁶¹, Venla Kurra^{62

63}, Triin Laisk⁵, Jari Laukkanen^{61

64}, Nathan Lawless²⁶, Aoxing Liu¹, Simonne Longerich⁴², Reedik Mägi⁵, Johanna Mäkelä⁶⁵, Antti Mäkitie^{66

67}, Anders Malarstig^{68

69}, Arto Mannermaa^{59

60}, Joseph Maranville²³, Athena Matakidou⁷⁰, Tuomo Meretoja⁴⁷, Sahar V Mozaffari³¹, Mari E K Niemi¹, Marianna Niemi^{19

71}, Teemu Niiranen^{6

72}, Christopher J O Donnell⁷³, Ma En Obeidat⁷³, George Okafo²⁶, Hanna M Ollila^{1

74}, Antti Palomäki⁷², Tuula Palotie^{75

76}, Jukka Partanen^{21

77}, Dirk S Paul⁷⁰, Margit Pelkonen⁷⁸, Rion K Pendergrass⁴⁵, Slavé Petrovski⁷⁰, Anne Pitkäranta⁷⁹, Adam Platt⁸⁰, David Pulford⁸¹, Eero Punkka¹⁰, Pirkko Pussinen⁷⁶, Neha Raghavan⁴², Fedik Rahimov⁴⁶, Deepak Rajpal⁵⁸, Nicole A Renaud⁷³, Bridget Riley-Gillis⁴⁶, Rodosthenis Rodosthenous¹, Elmo Saarentaus¹, Aino Salminen⁷⁶, Eveliina Salminen^{67

82}, Veikko Salomaa⁶, Johanna Schleutker³², Raisa Serpi⁵⁰, Huei-Yi Shen¹, Richard Siegel⁸³, Kaisa Silander⁶, Sanna Siltanen⁸⁴, Sirpa Soini⁶, Hilkka Soininen⁸⁵, Jae Hoon Sul⁴², Ioanna Tachmazidou⁷⁰, Kaisa Tasanen^{43

44}, Pentti Tienari^{86

87}, Sanna Toppila-Salmi⁸⁸, Taru Tukiainen¹, Tiinamaija Tuomi^{1

89

90

91}, Joni A Turunen^{47

92}, Jacob C Ulirsch^{2

3}, Felix Vaura^{6

93}, Petri Virolainen³², Jeffrey Waring⁴⁶, Dawn Waterworth⁹⁴, Robert Yang⁹⁵, Mari Nelis⁹⁶, Anu Reigo⁵, Andres Metspalu⁵, Lili Milani⁵, Tõnu Esko⁵, Caroline Fox⁴², Aki S Havulinna^{1

6}, Markus Perola⁶, Samuli Ripatti¹, Anu Jalanko¹, Tarja Laitinen⁸⁴, Tomi P Mäkelä⁹⁷, Robert Plenge²³, Mark McCarthy⁴⁵, Heiko Runz²⁵, Mark J Daly^{1

2

3

4}, Aarno Palotie^{98

99

100

101}

Affiliations

¹ Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
² Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
³ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
⁶ Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
⁷ Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland.
⁹ Faculty of Medicine and Health Technology, Center for Child, Adolescent and Maternal Health, University of Tampere, Tampere, Finland.
¹⁰ Helsinki Biobank, University of Helsinki and Hospital District of Helsinki and Uusimaa, Helsinki, Finland.
¹¹ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹² Digital Health Center, Hasso Plattner Institute for Digital Engineering, University of Potsdam Potsdam, Potsdam, Germany.
¹³ Hasso Plattner Institute for Digital Health at Mount Sinai, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ TAUCHI Research Center, Faculty of Information Technology and Communication Sciences, Tampere University, Tampere, Finland.
¹⁵ Translational Biology, Research and Development, Biogen, Cambridge, MA, USA.
¹⁶ BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁷ Optima Partners, Edinburgh, UK.
¹⁸ MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
¹⁹ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
²⁰ Institute of Computer Science, University of Tartu, Tartu, Estonia.
²¹ Finnish Red Cross Blood Service, Helsinki, Finland.
²² GlaxoSmithKline, Espoo, Finland.
²³ Bristol Myers Squibb, New York, NY, USA.
²⁴ Tampere University Hospital and Tampere University, Tampere, Finland.
²⁵ Biogen, Cambridge, MA, USA.
²⁶ Boehringer Ingelheim, Ingelheim am Rhein, Germany.
²⁷ GlaxoSmithKline, Collegeville, PA, USA.
²⁸ Division of Rheumatology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
²⁹ Orton Orthopedic Hospital, Helsinki, Finland.
³⁰ Abdominal Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland.
³¹ Maze Therapeutics, South San Francisco, CA, USA.
³² Auria Biobank, University of Turku and Turku University Hospital, Turku, Finland.
³³ FINBB, Finnish Biobank Cooperative, Helsinki, Finland.
³⁴ Pfizer, New York, NY, USA.
³⁵ Department of Medicine, Karolinska Institute, Solna, Sweden.
³⁶ Clinical Biobank Tampere, Tampere University and Tampere University Hospital, Tampere, Finland.
³⁷ Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu, Oulu, Finland.
³⁸ Biocenter Oulu, University of Oulu, Oulu, Finland.
³⁹ Oulu University Hospital, Oulu, Finland.
⁴⁰ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴¹ SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴² Merck & Co, Kenilworth, NJ, USA.
⁴³ PEDEGO Research Unit, University of Oulu, Oulu, Finland.
⁴⁴ Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.
⁴⁵ Genentech, San Francisco, CA, USA.
⁴⁶ AbbVie, Chicago, IL, USA.
⁴⁷ Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁴⁸ Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland.
⁴⁹ Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.
⁵⁰ Northern Finland Biobank Borealis, University of Oulu, Northern Ostrobothnia Hospital District, Oulu, Finland.
⁵¹ Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
⁵² Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁵³ Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
⁵⁴ Epilepsy Center, Kuopio University Hospital, Kuopio, Finland.
⁵⁵ Department of Neurology, University of Eastern Finland, Kuopio, Finland.
⁵⁶ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁵⁷ Computational Medicine, Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
⁵⁸ Translational Sciences, Sanofi R&D, Framingham, MA, USA.
⁵⁹ Biobank of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
⁶⁰ Kuopio University Hospital, Kuopio, Finland.
⁶¹ Central Finland Biobank, Central Finland Health Care District, Jyväskylä, Finland.
⁶² Department of Clinical Genetics, Tampere University Hospital, Tampere, Finland.
⁶³ Department of Clinical Genetics, Faculty of Medicine and Health Technology, Tampere, Finland.
⁶⁴ Department of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁶⁵ FINBB, Finnish Biobank Cooperative, Turku, Finland.
⁶⁶ Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki, Helsinki, Finland.
⁶⁷ Helsinki University Hospital, Helsinki, Finland.
⁶⁸ Pfizer, Cambridge, MA, USA.
⁶⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Solna, Sweden.
⁷⁰ Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁷¹ TAUCHI Research Center & Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁷² Turku University Hospital and University of Turku, Turku, Finland.
⁷³ Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
⁷⁴ Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁷⁵ Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland.
⁷⁶ Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
⁷⁷ Finnish Hematological Biobank, Helsinki, Finland.
⁷⁸ Department of Pulmonary Diseases, Kuopio University Hospital, Kuopio, Finland.
⁷⁹ Department of Otorhinolaryngology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁸⁰ Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁸¹ GlaxoSmithKline, Stevenage, UK.
⁸² Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center, University of Helsinki, Helsinki, Finland.
⁸³ Novartis Institutes for BioMedical Research, Basel, Switzerland.
⁸⁴ Finnish Clinical Biobank Tampere, Tampere University and Tampere University Hospital, Tampere, Finland.
⁸⁵ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁸⁶ Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
⁸⁷ Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
⁸⁸ Department of Allergy, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁸⁹ Abdominal Center, Endocrinology, Helsinki University Hospital, Helsinki, Finland.
⁹⁰ Folkhalsan Research Center, Helsinki, Finland.
⁹¹ Research Program of Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
⁹² Eye Genetics Group, Folkhälsan Research Center, Helsinki, Finland.
⁹³ University of Turku, Turku, Finland.
⁹⁴ Janssen Research & Development, Spring House, PA, USA.
⁹⁵ Janssen Biotech, Beerse, Belgium.
⁹⁶ Genomics Core Facility, Institute of Genomics, University of Tartu, Tartu, Estonia.
⁹⁷ Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
⁹⁸ Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. aarno.palotie@helsinki.fi.
⁹⁹ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. aarno.palotie@helsinki.fi.
¹⁰⁰ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. aarno.palotie@helsinki.fi.
¹⁰¹ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. aarno.palotie@helsinki.fi.

PMID: 36653562
PMCID: PMC9849126
DOI: 10.1038/s41586-022-05473-8

FinnGen provides genetic insights from a well-phenotyped isolated population

Mitja I Kurki et al. Nature. 2023 Jan.

. 2023 Jan;613(7944):508-518.

doi: 10.1038/s41586-022-05473-8. Epub 2023 Jan 18.

Authors

Affiliations

¹ Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
² Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
³ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
⁵ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
⁶ Finnish Institute for Health and Welfare (THL), Helsinki, Finland.
⁷ Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland.
⁹ Faculty of Medicine and Health Technology, Center for Child, Adolescent and Maternal Health, University of Tampere, Tampere, Finland.
¹⁰ Helsinki Biobank, University of Helsinki and Hospital District of Helsinki and Uusimaa, Helsinki, Finland.
¹¹ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹² Digital Health Center, Hasso Plattner Institute for Digital Engineering, University of Potsdam Potsdam, Potsdam, Germany.
¹³ Hasso Plattner Institute for Digital Health at Mount Sinai, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁴ TAUCHI Research Center, Faculty of Information Technology and Communication Sciences, Tampere University, Tampere, Finland.
¹⁵ Translational Biology, Research and Development, Biogen, Cambridge, MA, USA.
¹⁶ BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹⁷ Optima Partners, Edinburgh, UK.
¹⁸ MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
¹⁹ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
²⁰ Institute of Computer Science, University of Tartu, Tartu, Estonia.
²¹ Finnish Red Cross Blood Service, Helsinki, Finland.
²² GlaxoSmithKline, Espoo, Finland.
²³ Bristol Myers Squibb, New York, NY, USA.
²⁴ Tampere University Hospital and Tampere University, Tampere, Finland.
²⁵ Biogen, Cambridge, MA, USA.
²⁶ Boehringer Ingelheim, Ingelheim am Rhein, Germany.
²⁷ GlaxoSmithKline, Collegeville, PA, USA.
²⁸ Division of Rheumatology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
²⁹ Orton Orthopedic Hospital, Helsinki, Finland.
³⁰ Abdominal Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland.
³¹ Maze Therapeutics, South San Francisco, CA, USA.
³² Auria Biobank, University of Turku and Turku University Hospital, Turku, Finland.
³³ FINBB, Finnish Biobank Cooperative, Helsinki, Finland.
³⁴ Pfizer, New York, NY, USA.
³⁵ Department of Medicine, Karolinska Institute, Solna, Sweden.
³⁶ Clinical Biobank Tampere, Tampere University and Tampere University Hospital, Tampere, Finland.
³⁷ Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu, Oulu, Finland.
³⁸ Biocenter Oulu, University of Oulu, Oulu, Finland.
³⁹ Oulu University Hospital, Oulu, Finland.
⁴⁰ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴¹ SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴² Merck & Co, Kenilworth, NJ, USA.
⁴³ PEDEGO Research Unit, University of Oulu, Oulu, Finland.
⁴⁴ Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.
⁴⁵ Genentech, San Francisco, CA, USA.
⁴⁶ AbbVie, Chicago, IL, USA.
⁴⁷ Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁴⁸ Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland.
⁴⁹ Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.
⁵⁰ Northern Finland Biobank Borealis, University of Oulu, Northern Ostrobothnia Hospital District, Oulu, Finland.
⁵¹ Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
⁵² Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁵³ Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
⁵⁴ Epilepsy Center, Kuopio University Hospital, Kuopio, Finland.
⁵⁵ Department of Neurology, University of Eastern Finland, Kuopio, Finland.
⁵⁶ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁵⁷ Computational Medicine, Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
⁵⁸ Translational Sciences, Sanofi R&D, Framingham, MA, USA.
⁵⁹ Biobank of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
⁶⁰ Kuopio University Hospital, Kuopio, Finland.
⁶¹ Central Finland Biobank, Central Finland Health Care District, Jyväskylä, Finland.
⁶² Department of Clinical Genetics, Tampere University Hospital, Tampere, Finland.
⁶³ Department of Clinical Genetics, Faculty of Medicine and Health Technology, Tampere, Finland.
⁶⁴ Department of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁶⁵ FINBB, Finnish Biobank Cooperative, Turku, Finland.
⁶⁶ Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki, Helsinki, Finland.
⁶⁷ Helsinki University Hospital, Helsinki, Finland.
⁶⁸ Pfizer, Cambridge, MA, USA.
⁶⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Solna, Sweden.
⁷⁰ Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁷¹ TAUCHI Research Center & Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁷² Turku University Hospital and University of Turku, Turku, Finland.
⁷³ Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
⁷⁴ Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁷⁵ Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland.
⁷⁶ Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
⁷⁷ Finnish Hematological Biobank, Helsinki, Finland.
⁷⁸ Department of Pulmonary Diseases, Kuopio University Hospital, Kuopio, Finland.
⁷⁹ Department of Otorhinolaryngology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁸⁰ Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁸¹ GlaxoSmithKline, Stevenage, UK.
⁸² Department of Clinical Genetics, HUSLAB, HUS Diagnostic Center, University of Helsinki, Helsinki, Finland.
⁸³ Novartis Institutes for BioMedical Research, Basel, Switzerland.
⁸⁴ Finnish Clinical Biobank Tampere, Tampere University and Tampere University Hospital, Tampere, Finland.
⁸⁵ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁸⁶ Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
⁸⁷ Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
⁸⁸ Department of Allergy, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁸⁹ Abdominal Center, Endocrinology, Helsinki University Hospital, Helsinki, Finland.
⁹⁰ Folkhalsan Research Center, Helsinki, Finland.
⁹¹ Research Program of Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
⁹² Eye Genetics Group, Folkhälsan Research Center, Helsinki, Finland.
⁹³ University of Turku, Turku, Finland.
⁹⁴ Janssen Research & Development, Spring House, PA, USA.
⁹⁵ Janssen Biotech, Beerse, Belgium.
⁹⁶ Genomics Core Facility, Institute of Genomics, University of Tartu, Tartu, Estonia.
⁹⁷ Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
⁹⁸ Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. aarno.palotie@helsinki.fi.
⁹⁹ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. aarno.palotie@helsinki.fi.
¹⁰⁰ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. aarno.palotie@helsinki.fi.
¹⁰¹ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. aarno.palotie@helsinki.fi.

PMID: 36653562
PMCID: PMC9849126
DOI: 10.1038/s41586-022-05473-8

Erratum in

Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population.
Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, Reeve MP, Laivuori H, Aavikko M, Kaunisto MA, Loukola A, Lahtela E, Mattsson H, Laiho P, Della Briotta Parolo P, Lehisto AA, Kanai M, Mars N, Rämö J, Kiiskinen T, Heyne HO, Veerapen K, Rüeger S, Lemmelä S, Zhou W, Ruotsalainen S, Pärn K, Hiekkalinna T, Koskelainen S, Paajanen T, Llorens V, Gracia-Tabuenca J, Siirtola H, Reis K, Elnahas AG, Sun B, Foley CN, Aalto-Setälä K, Alasoo K, Arvas M, Auro K, Biswas S, Bizaki-Vallaskangas A, Carpen O, Chen CY, Dada OA, Ding Z, Ehm MG, Eklund K, Färkkilä M, Finucane H, Ganna A, Ghazal A, Graham RR, Green EM, Hakanen A, Hautalahti M, Hedman ÅK, Hiltunen M, Hinttala R, Hovatta I, Hu X, Huertas-Vazquez A, Huilaja L, Hunkapiller J, Jacob H, Jensen JN, Joensuu H, John S, Julkunen V, Jung M, Junttila J, Kaarniranta K, Kähönen M, Kajanne R, Kallio L, Kälviäinen R, Kaprio J; FinnGen; Kerimov N, Kettunen J, Kilpeläinen E, Kilpi T, Klinger K, Kosma VM, Kuopio T, Kurra V, Laisk T, Laukkanen J, Lawless N, Liu A, Longerich S, Mägi R, Mäkelä J, Mäkitie A, Malarstig A, Mannermaa A, Maranville J, Matakidou A, Meretoja T, Mozaffari SV, Niemi MEK, Niemi M, Niiranen T, O Donnell CJ, Obeidat… See abstract for full author list ➔ Kurki MI, et al. Nature. 2023 Mar;615(7952):E19. doi: 10.1038/s41586-023-05837-8. Nature. 2023. PMID: 36829046 Free PMC article. No abstract available.

Abstract

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored^1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10^-11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.

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Conflict of interest statement

J.C.U.: has received compensation for consulting from Goldfinch Bio and is an employee of Patch Biosciences. K.E.: Consultation fees from Sobi, and Orion corporation. A. Palomäki: consulting fee from Abbvie, Amgen and Pfizer, lecture fee from Pfizer and Sanofi. H. Jacob: employee of AbbVie. F.R.: employee of AbbVie. B.R.-G.: employee of AbbVie. J.W.: employee of AbbVie. A. Matakidou: employee of AstraZeneca. D.S.P.: employee of AstraZeneca. S.P.: employee of AstraZeneca. A. Platt: employee of AstraZeneca. I.T.: employee of AstraZeneca. B.S.: employee of Biogen. C.-Y.C.: employee of Biogen. S.J.: employee of Biogen. H.R.: employee of Biogen. Z.D.: employee of Boehringer Ingelheim. J.-N.J.: employee of Boehringer Ingelheim. M.J.: employee of Boehringer Ingelheim. N.L.: employee of Boehringer Ingelheim. G.O.: employee of Boehringer Ingelheim. S.B.: employee of Bristol Myers Squibb. J. Maranville: employee of Bristol Myers Squibb. R.P.: employee of Bristol Myers Squibb. J.H.: employee of Genentech. R.K.P.: employee of Genentech. M.M.: employee of Genentech. K. Auro: employee of GlaxoSmithKline. M.G.E.: employee of GlaxoSmithKline. D.P.: employee of GlaxoSmithKline. R.Y.: employee of Janssen Biotech. D.W.: employee of Janssen Research & Development. R.R.G.: employee of Maze Therapeutics. E.M.G.: employee of Maze Therapeutics. S.V.M.: employee of Maze Therapeutics. A.H.-V.: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. S. Longerich: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. N.R.: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J.H.S.: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. C.F.: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. M.E.K.N.: employee of Novartis. C.J.O.: employee of Novartis. M.O.: employee of Novartis. N.R.: employee of Novartis. R. Siegel: employee of Novartis. Å.K.H.: employee of Pfizer. X.H.: employee of Pfizer. A. Malarstig: employee of Pfizer. K. Klinger: employee of Sanofi. D.R.: employee of Sanofi. J.P.: employee of the Finnish Red Cross Blood Service. A.G.E.: employee of University of Tartu. M.J.D.: founder of Maze Therapeutics. T. Kuopio: lecture fee from Amgen, Roche and MSD. J.A.T.: lecture fee from Blueprint Genetics Finland, and on the advisory board of Novartis Finland (unrelated to this work). P.T.: lecture or consulting fee from Alexion, Roche, Merck, Janssen-Cilag, Novartis and Biogen (unrelated to this work). M. Aavikko: lecturing fee and congress trip reimbursement from Ipsen and Novartis (unrelated to this work). A. Palotie: member of the Pfizer Genetics Scientific Advisory Panel. V.S.: received a honorarium from Sanofi for consulting, and ongoing research collaboration with Bayer (all unrelated to the present study). H. Joensuu: senior consultant for Orion Pharma Orion, Chairman of the Scientific Advisory Board in Neutron Therapeutics, received a fee for acting as the Chair of an ESMO meeting from Deciphera Pharmaceuticals, stock ownership in Orion Pharma and Sartar Therapeutics. The other authors declare no competing interests.

Figures

**Fig. 1. FinnGen sample collection and phenotyping.**
a, Samples collected from different geographical areas. The map of Finland is divided into major administrative areas. Coloured regions represent the areas of the nine biobanks that provide samples to FinnGen. The Finnish Institute for Health and Welfare (THL), the Blood Service and the Terveystalo biobanks are not regional. The circle size represents relative sample sizes. The number of samples given are those used in the analyses after QC. b, National registries utilized to construct FinnGen end points. The numbers indicate the number of events in each register at the time of FinnGen release. An individual can have multiple diagnoses and can have events from multiple registers contributing to the end point of the individual. c, Sample prevalence of major disease categories in FinnGen. Major diseases for each category were chosen for demonstration purposes (Supplementary Tables 3 and 4). d, Examples of registers used for constructing four selected end points. The y axis represents individuals with matching register code in each register according to FinnGen end point definitions. Each individual can contribute only once to each register but the same individual can be counted in multiple registers. e, Comparison of effect sizes (beta values) in known genome-wide significant loci between four example FinnGen end points and large reference GWAS. The y and x axes represent FinnGen and reference GWAS beta values respectively. Beta values are aligned to be positive in reference studies. Lines extending from points indicate standard errors of beta values. Regression lines omit intercept and two types of regressions are provided: unweighted and weighted by pooled standard errors from the two studies. Solid line indicates identity line and dotted line and dashed lines indicate unweighted and weighted regression, respectively. Sample sizes used for e are given in Supplementary Table 7. Only variants with P < 1 × 10⁻¹⁰ in reference study were included. A comparison of all 15 diseases is provided in the Supplementary Information. Part a adapted with permission from an original biobank map created by BBMRI.fi.

**Fig. 2. Comparison of previously unknown and known lead variants in loci identified in the 15 studied diseases.**
a, Case prevalence and counts in FinnGen, the EstBB and the UKBB. The phenotypes are sorted on the basis of FinnGen prevalence. b, Distribution of minor AFs in known (red) and new (blue) loci in the NFSEE population. c, Distribution of AF enrichment between Finland and other Northwestern European populations in gnomAD (excluding Estonia and Sweden). The x axis represents enrichment bins. d, AFs of 25 replicated genome-wide significant (in FinnGen discovery) new low-frequency (<5% in NFSEE populations) variants in FinnGen, the EstBB and the UKBB. The dotted line indicates the same variants and no line means absence of the variant in other biobanks.

**Fig. 3. Characteristics of unique associations in end points identified in FinnGen.**
Characteristics of 493 (73 with coding variants in the credible set) specific associations in 112 (42 end points with coding variants in the credible set) end points identified in FinnGen release 5. Note that 25 of the associations with a coding variant with PIP < 0.05 in credible sets were removed from plots as ‘uncertain to contain coding variant’. a, Distribution of fine-mapping PIP values of the 73 coding variants. b, AF spectrum in associations with and without coding variants in credible sets (CS). c, Proportion of coding variants identified in different AFs (in NFSEE individuals in gnomAD). The numbers above the bars indicate the number of associations within a bin, the y axis indicates the proportion of associations with coding variants in their credible sets. d, Enrichment in Finland as a function of AF in the gnomAD NFSEE population (enrichment value for variants with AF values of 0 in NFEE individuals in gnomAD was set to maximum observed enrichment value of log₂(166) = 7.38). The smoothed regression lines of local average enrichment are estimated by local polynomial fitting (loess) and the shaded areas represent 95% confidence intervals of the model fit.

**Extended Data Fig. 1. FinnGen Age Distribution and Registers.**
A) Distribution of the current age (age at the end of the follow-up) and age of death for FinnGen participants B) Follow-up time and main coding used in each register among FinnGen participants in FinnGen release 5. Abbreviations: CANCER = The Finnish Cancer Registry; DEATH = Cause of death register; INPATIENT = HILMO - Care Register for Health Care: Inpatient hospital visits; OUTPATIENT = HILMO - Care Register for Health Care: Specialty outpatient visits and day surgeries; PURCHASE = Drug Purchases: All Prescription drug purchases; REIMBURSEMENT = Drug Reimbursement: entitlements for prescription drug reimbursement for certain chronic diseases.

**Extended Data Fig. 2. PCA classification of 224,737 FinnGen participants combined with 1000 genomes samples (AFR,AMR,EAST,EUR,FIN,SAS).**
FinnGen outlier samples were removed as deviating from the bulk of the FinnGen samples.

**Extended Data Fig. 3. Comparison of effect sizes between biobanks.**
A,B) Effect size (log(OR), beta) comparison of 275 genome-wide significant lead variants identified in FinnGen among 15 analysed diseases in Estonia and UKBB. The sign of beta is aligned to be positive in Estonia and UKBB. C,D) beta comparison of variants only in known loci. E,F) beta comparison of novel loci. Dashed lines indicates identity line and solid lines are the regression line (red line and text weighted by pooled standard error of betas).

**Extended Data Fig. 4. Enrichment of 493 unique phenome-wide significant associations binned by NFSEE MAF and split by whether 95% credible sets contain a coding variant.**
The p-values of the test of difference in average enrichment are shown on the right side of each MAF bin. Lines indicate 95% confidence interval of the mean enrichment. Number of coding/non-coding variants in each bin : 21/27, 12/35, 11/22, 3/10, 7/24 and 19/277 given in the same order as in the figure x-axis.

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Comment in

The FinnGen study: disease insights from a 'bottlenecked' population.
Minton K. Minton K. Nat Rev Genet. 2023 Apr;24(4):207. doi: 10.1038/s41576-023-00584-y. Nat Rev Genet. 2023. PMID: 36747004 No abstract available.

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References

1. Lim ET, et al. Distribution and medical impact of loss-of-function variants in the Finnish founder population. PLoS Genet. 2014;10:e1004494. doi: 10.1371/journal.pgen.1004494. - DOI - PMC - PubMed
1. Xue Y, et al. Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations. Nat. Commun. 2017;8:15927. doi: 10.1038/ncomms15927. - DOI - PMC - PubMed
1. Zuk, O. et al. Searching for missing heritability: designing rare variant association studies. Proc. Natl Acad. Sci. USA10.1073/pnas.1322563111 (2014). - PMC - PubMed
1. Norio R. The Finnish Disease Heritage III: the individual diseases. Hum. Genet. 2003;112:470–526. doi: 10.1007/s00439-002-0877-1. - DOI - PubMed
1. Auton A, et al. A global reference for human genetic variation. Nature. 2015;526:68–74. doi: 10.1038/nature15393. - DOI - PMC - PubMed

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[1] Lim ET, et al. Distribution and medical impact of loss-of-function variants in the Finnish founder population. PLoS Genet. 2014;10:e1004494. doi: 10.1371/journal.pgen.1004494. - DOI - PMC - PubMed

[2] Lim ET, et al. Distribution and medical impact of loss-of-function variants in the Finnish founder population. PLoS Genet. 2014;10:e1004494. doi: 10.1371/journal.pgen.1004494. - DOI - PMC - PubMed

[3] Xue Y, et al. Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations. Nat. Commun. 2017;8:15927. doi: 10.1038/ncomms15927. - DOI - PMC - PubMed

[4] Xue Y, et al. Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations. Nat. Commun. 2017;8:15927. doi: 10.1038/ncomms15927. - DOI - PMC - PubMed

[5] Zuk, O. et al. Searching for missing heritability: designing rare variant association studies. Proc. Natl Acad. Sci. USA10.1073/pnas.1322563111 (2014). - PMC - PubMed

[6] Zuk, O. et al. Searching for missing heritability: designing rare variant association studies. Proc. Natl Acad. Sci. USA10.1073/pnas.1322563111 (2014). - PMC - PubMed

[7] Norio R. The Finnish Disease Heritage III: the individual diseases. Hum. Genet. 2003;112:470–526. doi: 10.1007/s00439-002-0877-1. - DOI - PubMed

[8] Norio R. The Finnish Disease Heritage III: the individual diseases. Hum. Genet. 2003;112:470–526. doi: 10.1007/s00439-002-0877-1. - DOI - PubMed

[9] Auton A, et al. A global reference for human genetic variation. Nature. 2015;526:68–74. doi: 10.1038/nature15393. - DOI - PMC - PubMed

[10] Auton A, et al. A global reference for human genetic variation. Nature. 2015;526:68–74. doi: 10.1038/nature15393. - DOI - PMC - PubMed

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FinnGen provides genetic insights from a well-phenotyped isolated population

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FinnGen provides genetic insights from a well-phenotyped isolated population

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