About the Authors
- Niina Sandholm
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Contributed equally to this work with: Niina Sandholm, Rany M. Salem, Amy Jayne McKnight, Eoin P. Brennan
Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, Finland
- Rany M. Salem
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Contributed equally to this work with: Niina Sandholm, Rany M. Salem, Amy Jayne McKnight, Eoin P. Brennan
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Endocrine Research Unit, Department of Endocrinology, Children's Hospital, Boston, Massachusetts, United States of America, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
- Amy Jayne McKnight
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Contributed equally to this work with: Niina Sandholm, Rany M. Salem, Amy Jayne McKnight, Eoin P. Brennan
Affiliation Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom
- Eoin P. Brennan
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Contributed equally to this work with: Niina Sandholm, Rany M. Salem, Amy Jayne McKnight, Eoin P. Brennan
Affiliations Diabetes Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland, Mater Misericordiae Hospital, Dublin, Ireland
- Carol Forsblom
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Tamara Isakova
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Affiliation Division of Nephrology and Hypertension, University of Miami, Miami, Florida, United States of America
- Gareth J. McKay
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Affiliation Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom
- Winfred W. Williams
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Affiliations Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Denise M. Sadlier
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Affiliations Diabetes Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland, Mater Misericordiae Hospital, Dublin, Ireland
- Ville-Petteri Mäkinen
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, Institute of Clinical Medicine, Department of Internal Medicine, Biocenter Oulu and Clinical Research Center, University of Oulu, Oulu, Finland
- Elizabeth J. Swan
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Affiliation Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom
- Cameron Palmer
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Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Endocrine Research Unit, Department of Endocrinology, Children's Hospital, Boston, Massachusetts, United States of America
- Andrew P. Boright
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Affiliation Department of Medicine, University of Toronto, Toronto, Canada
- Emma Ahlqvist
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Affiliation Department of Clinical Sciences, Diabetes, and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden
- Harshal A. Deshmukh
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Affiliation Wellcome Trust Centre for Molecular Medicine, University of Dundee, Dundee, Scotland, United Kingdom
- Benjamin J. Keller
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Affiliation Computer Science, Eastern Michigan University, Ypsilanti, Michigan, United States of America
- Huateng Huang
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Affiliation Division of Nephrology, Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
- Aila J. Ahola
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Emma Fagerholm
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Daniel Gordin
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Valma Harjutsalo
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland
- Bing He
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Affiliation Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Outi Heikkilä
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Kustaa Hietala
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland
- Janne Kytö
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland
- Päivi Lahermo
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Affiliation Institute for Molecular Medicine Finland, Helsinki, Finland
- Markku Lehto
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Raija Lithovius
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Anne-May Österholm
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Affiliation Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Maija Parkkonen
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Janne Pitkäniemi
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Affiliation Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland
- Milla Rosengård-Bärlund
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Markku Saraheimo
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Cinzia Sarti
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Affiliation Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland
- Jenny Söderlund
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Aino Soro-Paavonen
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Anna Syreeni
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Lena M. Thorn
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Heikki Tikkanen
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Affiliation Unit for Sports and Exercise Medicine, Institute of Clinical Medicine, University of Helsinki, Finland
- Nina Tolonen
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Karl Tryggvason
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Affiliation Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Jaakko Tuomilehto
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Affiliations Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland, South Ostrobothnia Central Hospital, Seinäjoki, Finland, Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain, Centre for Vascular Prevention, Danube-University Krems, Krems, Austria
- Johan Wadén
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Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- Geoffrey V. Gill
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Affiliation Diabetes Endocrine Unit, Clinical Sciences Centre, Aintree University Hospital, University of Liverpool, Liverpool, United Kingdom
- Sarah Prior
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Affiliation Institute of Life Sciences, Swansea University, Swansea, United Kingdom
- Candace Guiducci
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Affiliation Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America
- Daniel B. Mirel
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Affiliation Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America
- Andrew Taylor
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Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- S. Mohsen Hosseini
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Affiliations Institute of Medical Science, University of Toronto, Toronto, Canada, Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada
- DCCT/EDIC Research Group
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¶Membership of the DCCT/EDIC Research Group is provided in Table S14.
Affiliations National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland, United States of America, Biostatics Division, The George Washington University, Washington, D.C., United States of America
- Hans-Henrik Parving
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Affiliations Department of Medical Endocrinology, University Hospital of Copenhagen, Copenhagen, Denmark, Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
- Peter Rossing
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Affiliations Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark, Steno Diabetes Center, Gentofte, Denmark
- Lise Tarnow
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Affiliations Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark, Steno Diabetes Center, Gentofte, Denmark
- Claes Ladenvall
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Affiliation Department of Clinical Sciences, Diabetes, and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden
- François Alhenc-Gelas
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Affiliation INSERM U872, Paris-Descartes University, Pierre and Marie Curie University, Paris, France
- Pierre Lefebvre
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Affiliation CHU Sart Tilman, Liège, Belgium
- Vincent Rigalleau
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Affiliation CHU Bordeaux, Bordeaux, France
- Ronan Roussel
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Affiliations AP-HP, Hôpital Bichat, Diabetology Endocrinology Nutrition, Paris, France, Université Paris Diderot, Sorbonne Paris Cité, UMR 738, Paris, France, INSERM, UMR872, Equipe 2, Centre de Recherche des Cordeliers, Paris, France
- David-Alexandre Tregouet
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Affiliation INSERM UMR_S 937, ICAN Institute for Cardiometabolism and Nutrition, Pierre and Marie Curie University, Paris, France
- Anna Maestroni
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Affiliation Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milano, Italy
- Silvia Maestroni
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Affiliation Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milano, Italy
- Henrik Falhammar
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Affiliations Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Stockholm, Sweden
- Tianwei Gu
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Affiliation Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Anna Möllsten
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Affiliation Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden
- Danut Cimponeriu
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Affiliation Genetics Department, Bucharest University, Bucharest, Romania
- Mihai Ioana
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Affiliation University of Medicine and Pharmacy of Craiova, Craiova, Romania
- Maria Mota
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Affiliation University of Medicine and Pharmacy of Craiova, Craiova, Romania
- Eugen Mota
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Affiliation University of Medicine and Pharmacy of Craiova, Craiova, Romania
- Cristian Serafinceanu
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Affiliation “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Monica Stavarachi
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Affiliation Genetics Department, Bucharest University, Bucharest, Romania
- Robert L. Hanson
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Affiliation Diabetes Epidemiology and Clinical Research Section, NIDDK, Phoenix, Arizona, United States of America
- Robert G. Nelson
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Affiliation Diabetes Epidemiology and Clinical Research Section, NIDDK, Phoenix, Arizona, United States of America
- Matthias Kretzler
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Affiliation Internal Medicine, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America
- Helen M. Colhoun
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Affiliation Wellcome Trust Centre for Molecular Medicine, University of Dundee, Dundee, Scotland, United Kingdom
- Nicolae Mircea Panduru
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Affiliation “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Harvest F. Gu
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Affiliation Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Kerstin Brismar
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Affiliations Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Stockholm, Sweden
- Gianpaolo Zerbini
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Affiliation Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milano, Italy
- Samy Hadjadj
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Affiliations CHU Poitiers–Endocrinology, University of Poitiers, Poitiers, France, INSERM CIC0802, CHU Poitiers, Poitiers, France
- Michel Marre
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Affiliations AP-HP, Hôpital Bichat, Diabetology Endocrinology Nutrition, Paris, France, Université Paris Diderot, Sorbonne Paris Cité, UMR 738, Paris, France, INSERM, U695 (Genetic Determinants of Type 2 Diabetes and Its Vascular Complications), Paris, France
- Leif Groop
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Affiliation Department of Clinical Sciences, Diabetes, and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden
- Maria Lajer
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Affiliation Steno Diabetes Center, Gentofte, Denmark
- Shelley B. Bull
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Affiliations Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Canada, Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
- Daryl Waggott
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Affiliation Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Canada
- Andrew D. Paterson
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Affiliations Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada, Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
- David A. Savage
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Affiliation Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom
- Stephen C. Bain
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Affiliation Institute of Life Sciences, Swansea University, Swansea, United Kingdom
- Finian Martin
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Affiliations Diabetes Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland, Mater Misericordiae Hospital, Dublin, Ireland
- Joel N. Hirschhorn
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* E-mail: joelh@broadinstitute.org (JN Hirschhorn); catherine.godson@ucd.ie (C Godson); jcflorez@partners.org (JC Florez); per-henrik.groop@helsinki.fi (P-H Groop); a.p.maxwell@qub.ac.uk (AP Maxwell)
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Endocrine Research Unit, Department of Endocrinology, Children's Hospital, Boston, Massachusetts, United States of America, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
- Catherine Godson
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* E-mail: joelh@broadinstitute.org (JN Hirschhorn); catherine.godson@ucd.ie (C Godson); jcflorez@partners.org (JC Florez); per-henrik.groop@helsinki.fi (P-H Groop); a.p.maxwell@qub.ac.uk (AP Maxwell)
Affiliations Diabetes Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland, Mater Misericordiae Hospital, Dublin, Ireland
- Jose C. Florez
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* E-mail: joelh@broadinstitute.org (JN Hirschhorn); catherine.godson@ucd.ie (C Godson); jcflorez@partners.org (JC Florez); per-henrik.groop@helsinki.fi (P-H Groop); a.p.maxwell@qub.ac.uk (AP Maxwell)
Affiliations Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Per-Henrik Groop
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* E-mail: joelh@broadinstitute.org (JN Hirschhorn); catherine.godson@ucd.ie (C Godson); jcflorez@partners.org (JC Florez); per-henrik.groop@helsinki.fi (P-H Groop); a.p.maxwell@qub.ac.uk (AP Maxwell)
Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- Alexander P. Maxwell
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* E-mail: joelh@broadinstitute.org (JN Hirschhorn); catherine.godson@ucd.ie (C Godson); jcflorez@partners.org (JC Florez); per-henrik.groop@helsinki.fi (P-H Groop); a.p.maxwell@qub.ac.uk (AP Maxwell)
Affiliations Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom, Regional Nephrology Unit, Belfast City Hospital, Belfast, United Kingdom
Competing Interests
JC Florez has received consulting honoraria from Novartis, Lilly, and Pfizer. M Kretzler received grant support from Hoffman La Roche and Fibrotech. P-H Groop has received lecture honorariums from Abbot, Boehringer Ingelheim, Cebix, Eli Lilly, Genzyme, Novartis, Novo Nordisk, MSD, and research grants from Eli Lilly and Roche. P-H Groop is also an advisory board member of Boehringer Ingelheim and Novartis.
Author Contributions
Conceived and designed the experiments: AP Maxwell, JC Florez, JN Hirschhorn, P-H Groop, C Godson, F Martin, G Zerbini, M Marre, S Hadjadj, HF Gu, K Brismar, L Groop, NM Panduru, SC Bain, M Lajer, HM Colhoun, AD Paterson, D Waggott, SB Bull, M Kretzler. Performed the experiments: DA Savage, AJ McKnight, EJ Swan, C Guiducci, DB Mirel, A Taylor, C Godson, N Sandholm, M Parkkonen, J Söderlund, A Syreeni, P Lahermo, K Tryggvason, B He, A-M Österholm, AD Paterson, S Maestroni, S Hadjadj, M Marre, V Rigalleau, R Roussel, F Alhenc-Gelas, P Lefebvre, HF Gu, A Möllsten, T Gu, E Ahlqvist, M Ioana, M Stavarachi, D Cimponeriu, SM Hosseini, M Kretzler, RL Hanson. Analyzed the data: AJ McKnight, GJ McKay, EJ Swan, JC Florez, JN Hirschhorn, C Palmer, RM Salem, N Sandholm, C Forsblom, V-P Mäkinen, EP Brennan, F Martin, S Hadjadj, M Marre, V Rigalleau, R Roussel, F Alhenc-Gelas, P Lefebvre, D-A Tregouet, C Ladenvall, HA Deshmukh, AD Paterson, AP Boright, D Waggott, BJ Keller, H Huang, E Ahlqvist. Contributed reagents/materials/analysis tools: S Prior, SB Bull, GV Gill, AJ McKnight, AP Maxwell, T Isakova, WW Williams, N Sandholm, C Forsblom, V Harjutsalo, AJ Ahola, E Fagerholm, D Gordin, O Heikkilä, K Hietala, J Kytö, M Lehto, V-P Mäkinen, M Rosengård-Bärlund, LM Thorn, N Tolonen, M Saraheimo, A Soro-Paavonen, J Wadén, H Tikkanen, J Tuomilehto, P Lahermo, P-H Groop, J Pitkäniemi, C Sarti, K Tryggvason, B He, A-M Österholm, AD Paterson, DM Sadlier, G Zerbini, A Maestroni, HF Gu, A Möllsten, H Falhammar, E Ahlqvist, M Mota, EM, SC Bain, GV Gill, S Prior, M Lehto, L Tarnow, P Rossing, H-H Parving, HM Colhoun, HA Deshmukh, M Kretzler, RG Nelson, RL Hanson, R Lithovius, K Brismar. Wrote the paper: N Sandholm, RM Salem, AJ McKnight, EP Brennan, C Forsblom, T Isakova, GJ McKay, WW Williams, DM Sadlier, F Martin, JN Hirschhorn, C Godson, JC Florez, P-H Groop, AP Maxwell.