About the Authors

Niina Sandholm

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

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

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

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

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

Affiliation Division of Nephrology and Hypertension, University of Miami, Miami, Florida, United States of America

Gareth J. McKay

Affiliation Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom

Winfred W. Williams

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

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

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

Affiliation Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom

Cameron Palmer

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

Affiliation Department of Medicine, University of Toronto, Toronto, Canada

Emma Ahlqvist

Affiliation Department of Clinical Sciences, Diabetes, and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden

Harshal A. Deshmukh

Affiliation Wellcome Trust Centre for Molecular Medicine, University of Dundee, Dundee, Scotland, United Kingdom

Benjamin J. Keller

Affiliation Computer Science, Eastern Michigan University, Ypsilanti, Michigan, United States of America

Huateng Huang

Affiliation Division of Nephrology, Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America

Aila J. Ahola

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

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

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

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

Affiliation Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

Outi Heikkilä

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

Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland

Janne Kytö

Affiliations Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland

Päivi Lahermo

Affiliation Institute for Molecular Medicine Finland, Helsinki, Finland

Markku Lehto

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

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

Affiliation Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

Maija Parkkonen

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

Affiliation Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland

Milla Rosengård-Bärlund

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

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

Affiliation Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland

Jenny Söderlund

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

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

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

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

Affiliation Unit for Sports and Exercise Medicine, Institute of Clinical Medicine, University of Helsinki, Finland

Nina Tolonen

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

Affiliation Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

Jaakko Tuomilehto

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

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

Affiliation Diabetes Endocrine Unit, Clinical Sciences Centre, Aintree University Hospital, University of Liverpool, Liverpool, United Kingdom

Sarah Prior

Affiliation Institute of Life Sciences, Swansea University, Swansea, United Kingdom

Candace Guiducci

Affiliation Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America

Daniel B. Mirel

Affiliation Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America

Andrew Taylor

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

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

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

Affiliations Department of Medical Endocrinology, University Hospital of Copenhagen, Copenhagen, Denmark, Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

Peter Rossing

Affiliations Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark, Steno Diabetes Center, Gentofte, Denmark

Lise Tarnow

Affiliations Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark, Steno Diabetes Center, Gentofte, Denmark

Claes Ladenvall

Affiliation Department of Clinical Sciences, Diabetes, and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden

François Alhenc-Gelas

Affiliation INSERM U872, Paris-Descartes University, Pierre and Marie Curie University, Paris, France

Pierre Lefebvre

Affiliation CHU Sart Tilman, Liège, Belgium

Vincent Rigalleau

Affiliation CHU Bordeaux, Bordeaux, France

Ronan Roussel

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

Affiliation INSERM UMR_S 937, ICAN Institute for Cardiometabolism and Nutrition, Pierre and Marie Curie University, Paris, France

Anna Maestroni

Affiliation Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milano, Italy

Silvia Maestroni

Affiliation Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milano, Italy

Henrik Falhammar

Affiliations Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Stockholm, Sweden

Tianwei Gu

Affiliation Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Anna Möllsten

Affiliation Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden

Danut Cimponeriu

Affiliation Genetics Department, Bucharest University, Bucharest, Romania

Mihai Ioana

Affiliation University of Medicine and Pharmacy of Craiova, Craiova, Romania

Maria Mota

Affiliation University of Medicine and Pharmacy of Craiova, Craiova, Romania

Eugen Mota

Affiliation University of Medicine and Pharmacy of Craiova, Craiova, Romania

Cristian Serafinceanu

Affiliation “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Monica Stavarachi

Affiliation Genetics Department, Bucharest University, Bucharest, Romania

Robert L. Hanson

Affiliation Diabetes Epidemiology and Clinical Research Section, NIDDK, Phoenix, Arizona, United States of America

Robert G. Nelson

Affiliation Diabetes Epidemiology and Clinical Research Section, NIDDK, Phoenix, Arizona, United States of America

Matthias Kretzler

Affiliation Internal Medicine, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America

Helen M. Colhoun

Affiliation Wellcome Trust Centre for Molecular Medicine, University of Dundee, Dundee, Scotland, United Kingdom

Nicolae Mircea Panduru

Affiliation “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Harvest F. Gu

Affiliation Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Kerstin Brismar

Affiliations Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Stockholm, Sweden

Gianpaolo Zerbini

Affiliation Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milano, Italy

Samy Hadjadj

Affiliations CHU Poitiers–Endocrinology, University of Poitiers, Poitiers, France, INSERM CIC0802, CHU Poitiers, Poitiers, France

Michel Marre

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

Affiliation Department of Clinical Sciences, Diabetes, and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden

Maria Lajer

Affiliation Steno Diabetes Center, Gentofte, Denmark

Shelley B. Bull

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

Affiliation Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Toronto, Canada

Andrew D. Paterson

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

Affiliation Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom

Stephen C. Bain

Affiliation Institute of Life Sciences, Swansea University, Swansea, United Kingdom

Finian Martin

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

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

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

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

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

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.