The Genetic Landscape of Renal Complications in Type 1 Diabetes.
Identifieur interne : 001177 ( PubMed/Corpus ); précédent : 001176; suivant : 001178The Genetic Landscape of Renal Complications in Type 1 Diabetes.
Auteurs : Niina Sandholm ; Natalie Van Zuydam ; Emma Ahlqvist ; Thorhildur Juliusdottir ; Harshal A. Deshmukh ; N William Rayner ; Barbara Di Camillo ; Carol Forsblom ; Joao Fadista ; Daniel Ziemek ; Rany M. Salem ; Linda T. Hiraki ; Marcus Pezzolesi ; David Trégouët ; Emma Dahlström ; Erkka Valo ; Nikolay Oskolkov ; Claes Ladenvall ; M Loredana Marcovecchio ; Jason Cooper ; Francesco Sambo ; Alberto Malovini ; Marco Manfrini ; Amy Jayne Mcknight ; Maria Lajer ; Valma Harjutsalo ; Daniel Gordin ; Maija Parkkonen ; Valeriya Lyssenko ; Paul M. Mckeigue ; Stephen S. Rich ; Mary Julia Brosnan ; Eric Fauman ; Riccardo Bellazzi ; Peter Rossing ; Samy Hadjadj ; Andrzej Krolewski ; Andrew D. Paterson ; Joel N. Hirschhorn ; Alexander P. Maxwell ; Claudio Cobelli ; Helen M. Colhoun ; Leif Groop ; Mark I. Mccarthy ; Per-Henrik GroopSource :
- Journal of the American Society of Nephrology : JASN [ 1533-3450 ] ; 2017.
English descriptors
- KwdEn :
- MESH :
- complications : Diabetes Mellitus, Type 1.
- genetics : Diabetes Mellitus, Type 1, Diabetic Nephropathies.
- Adolescent, Adult, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Young Adult.
Abstract
Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10(-5)) and the risk of type 2 diabetes (P=6.1×10(-4)) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10(-4)). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10(-6)), and pentose and glucuronate interconversions (P=3.0×10(-6)) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.
DOI: 10.1681/ASN.2016020231
PubMed: 27647854
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Genetic Landscape of Renal Complications in Type 1 Diabetes.</title><author><name sortKey="Sandholm, Niina" sort="Sandholm, Niina" uniqKey="Sandholm N" first="Niina" last="Sandholm">Niina Sandholm</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Van Zuydam, Natalie" sort="Van Zuydam, Natalie" uniqKey="Van Zuydam N" first="Natalie" last="Van Zuydam">Natalie Van Zuydam</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Ahlqvist, Emma" sort="Ahlqvist, Emma" uniqKey="Ahlqvist E" first="Emma" last="Ahlqvist">Emma Ahlqvist</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Juliusdottir, Thorhildur" sort="Juliusdottir, Thorhildur" uniqKey="Juliusdottir T" first="Thorhildur" last="Juliusdottir">Thorhildur Juliusdottir</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Deshmukh, Harshal A" sort="Deshmukh, Harshal A" uniqKey="Deshmukh H" first="Harshal A" last="Deshmukh">Harshal A. Deshmukh</name><affiliation><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Rayner, N William" sort="Rayner, N William" uniqKey="Rayner N" first="N William" last="Rayner">N William Rayner</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Di Camillo, Barbara" sort="Di Camillo, Barbara" uniqKey="Di Camillo B" first="Barbara" last="Di Camillo">Barbara Di Camillo</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Forsblom, Carol" sort="Forsblom, Carol" uniqKey="Forsblom C" first="Carol" last="Forsblom">Carol Forsblom</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Fadista, Joao" sort="Fadista, Joao" uniqKey="Fadista J" first="Joao" last="Fadista">Joao Fadista</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Ziemek, Daniel" sort="Ziemek, Daniel" uniqKey="Ziemek D" first="Daniel" last="Ziemek">Daniel Ziemek</name><affiliation><nlm:affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Salem, Rany M" sort="Salem, Rany M" uniqKey="Salem R" first="Rany M" last="Salem">Rany M. Salem</name><affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Hiraki, Linda T" sort="Hiraki, Linda T" uniqKey="Hiraki L" first="Linda T" last="Hiraki">Linda T. Hiraki</name><affiliation><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Pezzolesi, Marcus" sort="Pezzolesi, Marcus" uniqKey="Pezzolesi M" first="Marcus" last="Pezzolesi">Marcus Pezzolesi</name><affiliation><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Trégouët">David Trégouët</name><affiliation><nlm:affiliation>Sorbonne Universities, Pierre et Marie Curie University (UPMC) and National Institute for Health and Medical Research, Mixed Research Unit in Health (UMR_S) 1166, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dahlstrom, Emma" sort="Dahlstrom, Emma" uniqKey="Dahlstrom E" first="Emma" last="Dahlström">Emma Dahlström</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Valo, Erkka" sort="Valo, Erkka" uniqKey="Valo E" first="Erkka" last="Valo">Erkka Valo</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Oskolkov, Nikolay" sort="Oskolkov, Nikolay" uniqKey="Oskolkov N" first="Nikolay" last="Oskolkov">Nikolay Oskolkov</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Ladenvall, Claes" sort="Ladenvall, Claes" uniqKey="Ladenvall C" first="Claes" last="Ladenvall">Claes Ladenvall</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Marcovecchio, M Loredana" sort="Marcovecchio, M Loredana" uniqKey="Marcovecchio M" first="M Loredana" last="Marcovecchio">M Loredana Marcovecchio</name><affiliation><nlm:affiliation>Department of Paediatrics, Institute of Metabolic Science, and.</nlm:affiliation></affiliation></author><author><name sortKey="Cooper, Jason" sort="Cooper, Jason" uniqKey="Cooper J" first="Jason" last="Cooper">Jason Cooper</name><affiliation><nlm:affiliation>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Sambo, Francesco" sort="Sambo, Francesco" uniqKey="Sambo F" first="Francesco" last="Sambo">Francesco Sambo</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Malovini, Alberto" sort="Malovini, Alberto" uniqKey="Malovini A" first="Alberto" last="Malovini">Alberto Malovini</name><affiliation><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Manfrini, Marco" sort="Manfrini, Marco" uniqKey="Manfrini M" first="Marco" last="Manfrini">Marco Manfrini</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Mcknight, Amy Jayne" sort="Mcknight, Amy Jayne" uniqKey="Mcknight A" first="Amy Jayne" last="Mcknight">Amy Jayne Mcknight</name><affiliation><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Lajer, Maria" sort="Lajer, Maria" uniqKey="Lajer M" first="Maria" last="Lajer">Maria Lajer</name><affiliation><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Harjutsalo, Valma" sort="Harjutsalo, Valma" uniqKey="Harjutsalo V" first="Valma" last="Harjutsalo">Valma Harjutsalo</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Gordin, Daniel" sort="Gordin, Daniel" uniqKey="Gordin D" first="Daniel" last="Gordin">Daniel Gordin</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Parkkonen, Maija" sort="Parkkonen, Maija" uniqKey="Parkkonen M" first="Maija" last="Parkkonen">Maija Parkkonen</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Mckeigue, Paul M" sort="Mckeigue, Paul M" uniqKey="Mckeigue P" first="Paul M" last="Mckeigue">Paul M. Mckeigue</name><affiliation><nlm:affiliation>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S" last="Rich">Stephen S. Rich</name><affiliation><nlm:affiliation>Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Brosnan, Mary Julia" sort="Brosnan, Mary Julia" uniqKey="Brosnan M" first="Mary Julia" last="Brosnan">Mary Julia Brosnan</name><affiliation><nlm:affiliation>Cardiovascular and Metabolic Diseases Research Unit, and.</nlm:affiliation></affiliation></author><author><name sortKey="Fauman, Eric" sort="Fauman, Eric" uniqKey="Fauman E" first="Eric" last="Fauman">Eric Fauman</name><affiliation><nlm:affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Bellazzi, Riccardo" sort="Bellazzi, Riccardo" uniqKey="Bellazzi R" first="Riccardo" last="Bellazzi">Riccardo Bellazzi</name><affiliation><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name><affiliation><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Hadjadj, Samy" sort="Hadjadj, Samy" uniqKey="Hadjadj S" first="Samy" last="Hadjadj">Samy Hadjadj</name><affiliation><nlm:affiliation>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers, France.</nlm:affiliation></affiliation></author><author><name sortKey="Krolewski, Andrzej" sort="Krolewski, Andrzej" uniqKey="Krolewski A" first="Andrzej" last="Krolewski">Andrzej Krolewski</name><affiliation><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Paterson, Andrew D" sort="Paterson, Andrew D" uniqKey="Paterson A" first="Andrew D" last="Paterson">Andrew D. Paterson</name><affiliation><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Hirschhorn, Joel N" sort="Hirschhorn, Joel N" uniqKey="Hirschhorn J" first="Joel N" last="Hirschhorn">Joel N. Hirschhorn</name><affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Maxwell, Alexander P" sort="Maxwell, Alexander P" uniqKey="Maxwell A" first="Alexander P" last="Maxwell">Alexander P. Maxwell</name><affiliation><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Cobelli, Claudio" sort="Cobelli, Claudio" uniqKey="Cobelli C" first="Claudio" last="Cobelli">Claudio Cobelli</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Colhoun, Helen M" sort="Colhoun, Helen M" uniqKey="Colhoun H" first="Helen M" last="Colhoun">Helen M. Colhoun</name><affiliation><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Groop, Per Henrik" sort="Groop, Per Henrik" uniqKey="Groop P" first="Per-Henrik" last="Groop">Per-Henrik Groop</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; per-henrik.groop@helsinki.fi.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:27647854</idno><idno type="pmid">27647854</idno><idno type="doi">10.1681/ASN.2016020231</idno><idno type="wicri:Area/PubMed/Corpus">001177</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001177</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The Genetic Landscape of Renal Complications in Type 1 Diabetes.</title><author><name sortKey="Sandholm, Niina" sort="Sandholm, Niina" uniqKey="Sandholm N" first="Niina" last="Sandholm">Niina Sandholm</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Van Zuydam, Natalie" sort="Van Zuydam, Natalie" uniqKey="Van Zuydam N" first="Natalie" last="Van Zuydam">Natalie Van Zuydam</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Ahlqvist, Emma" sort="Ahlqvist, Emma" uniqKey="Ahlqvist E" first="Emma" last="Ahlqvist">Emma Ahlqvist</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Juliusdottir, Thorhildur" sort="Juliusdottir, Thorhildur" uniqKey="Juliusdottir T" first="Thorhildur" last="Juliusdottir">Thorhildur Juliusdottir</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Deshmukh, Harshal A" sort="Deshmukh, Harshal A" uniqKey="Deshmukh H" first="Harshal A" last="Deshmukh">Harshal A. Deshmukh</name><affiliation><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Rayner, N William" sort="Rayner, N William" uniqKey="Rayner N" first="N William" last="Rayner">N William Rayner</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Di Camillo, Barbara" sort="Di Camillo, Barbara" uniqKey="Di Camillo B" first="Barbara" last="Di Camillo">Barbara Di Camillo</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Forsblom, Carol" sort="Forsblom, Carol" uniqKey="Forsblom C" first="Carol" last="Forsblom">Carol Forsblom</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Fadista, Joao" sort="Fadista, Joao" uniqKey="Fadista J" first="Joao" last="Fadista">Joao Fadista</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Ziemek, Daniel" sort="Ziemek, Daniel" uniqKey="Ziemek D" first="Daniel" last="Ziemek">Daniel Ziemek</name><affiliation><nlm:affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Salem, Rany M" sort="Salem, Rany M" uniqKey="Salem R" first="Rany M" last="Salem">Rany M. Salem</name><affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Hiraki, Linda T" sort="Hiraki, Linda T" uniqKey="Hiraki L" first="Linda T" last="Hiraki">Linda T. Hiraki</name><affiliation><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Pezzolesi, Marcus" sort="Pezzolesi, Marcus" uniqKey="Pezzolesi M" first="Marcus" last="Pezzolesi">Marcus Pezzolesi</name><affiliation><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Trégouët">David Trégouët</name><affiliation><nlm:affiliation>Sorbonne Universities, Pierre et Marie Curie University (UPMC) and National Institute for Health and Medical Research, Mixed Research Unit in Health (UMR_S) 1166, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dahlstrom, Emma" sort="Dahlstrom, Emma" uniqKey="Dahlstrom E" first="Emma" last="Dahlström">Emma Dahlström</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Valo, Erkka" sort="Valo, Erkka" uniqKey="Valo E" first="Erkka" last="Valo">Erkka Valo</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Oskolkov, Nikolay" sort="Oskolkov, Nikolay" uniqKey="Oskolkov N" first="Nikolay" last="Oskolkov">Nikolay Oskolkov</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Ladenvall, Claes" sort="Ladenvall, Claes" uniqKey="Ladenvall C" first="Claes" last="Ladenvall">Claes Ladenvall</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Marcovecchio, M Loredana" sort="Marcovecchio, M Loredana" uniqKey="Marcovecchio M" first="M Loredana" last="Marcovecchio">M Loredana Marcovecchio</name><affiliation><nlm:affiliation>Department of Paediatrics, Institute of Metabolic Science, and.</nlm:affiliation></affiliation></author><author><name sortKey="Cooper, Jason" sort="Cooper, Jason" uniqKey="Cooper J" first="Jason" last="Cooper">Jason Cooper</name><affiliation><nlm:affiliation>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Sambo, Francesco" sort="Sambo, Francesco" uniqKey="Sambo F" first="Francesco" last="Sambo">Francesco Sambo</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Malovini, Alberto" sort="Malovini, Alberto" uniqKey="Malovini A" first="Alberto" last="Malovini">Alberto Malovini</name><affiliation><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Manfrini, Marco" sort="Manfrini, Marco" uniqKey="Manfrini M" first="Marco" last="Manfrini">Marco Manfrini</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Mcknight, Amy Jayne" sort="Mcknight, Amy Jayne" uniqKey="Mcknight A" first="Amy Jayne" last="Mcknight">Amy Jayne Mcknight</name><affiliation><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Lajer, Maria" sort="Lajer, Maria" uniqKey="Lajer M" first="Maria" last="Lajer">Maria Lajer</name><affiliation><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Harjutsalo, Valma" sort="Harjutsalo, Valma" uniqKey="Harjutsalo V" first="Valma" last="Harjutsalo">Valma Harjutsalo</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Gordin, Daniel" sort="Gordin, Daniel" uniqKey="Gordin D" first="Daniel" last="Gordin">Daniel Gordin</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Parkkonen, Maija" sort="Parkkonen, Maija" uniqKey="Parkkonen M" first="Maija" last="Parkkonen">Maija Parkkonen</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation></affiliation></author><author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Mckeigue, Paul M" sort="Mckeigue, Paul M" uniqKey="Mckeigue P" first="Paul M" last="Mckeigue">Paul M. Mckeigue</name><affiliation><nlm:affiliation>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S" last="Rich">Stephen S. Rich</name><affiliation><nlm:affiliation>Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.</nlm:affiliation></affiliation></author><author><name sortKey="Brosnan, Mary Julia" sort="Brosnan, Mary Julia" uniqKey="Brosnan M" first="Mary Julia" last="Brosnan">Mary Julia Brosnan</name><affiliation><nlm:affiliation>Cardiovascular and Metabolic Diseases Research Unit, and.</nlm:affiliation></affiliation></author><author><name sortKey="Fauman, Eric" sort="Fauman, Eric" uniqKey="Fauman E" first="Eric" last="Fauman">Eric Fauman</name><affiliation><nlm:affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Bellazzi, Riccardo" sort="Bellazzi, Riccardo" uniqKey="Bellazzi R" first="Riccardo" last="Bellazzi">Riccardo Bellazzi</name><affiliation><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name><affiliation><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Hadjadj, Samy" sort="Hadjadj, Samy" uniqKey="Hadjadj S" first="Samy" last="Hadjadj">Samy Hadjadj</name><affiliation><nlm:affiliation>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers, France.</nlm:affiliation></affiliation></author><author><name sortKey="Krolewski, Andrzej" sort="Krolewski, Andrzej" uniqKey="Krolewski A" first="Andrzej" last="Krolewski">Andrzej Krolewski</name><affiliation><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Paterson, Andrew D" sort="Paterson, Andrew D" uniqKey="Paterson A" first="Andrew D" last="Paterson">Andrew D. Paterson</name><affiliation><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Hirschhorn, Joel N" sort="Hirschhorn, Joel N" uniqKey="Hirschhorn J" first="Joel N" last="Hirschhorn">Joel N. Hirschhorn</name><affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Maxwell, Alexander P" sort="Maxwell, Alexander P" uniqKey="Maxwell A" first="Alexander P" last="Maxwell">Alexander P. Maxwell</name><affiliation><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Cobelli, Claudio" sort="Cobelli, Claudio" uniqKey="Cobelli C" first="Claudio" last="Cobelli">Claudio Cobelli</name><affiliation><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Colhoun, Helen M" sort="Colhoun, Helen M" uniqKey="Colhoun H" first="Helen M" last="Colhoun">Helen M. Colhoun</name><affiliation><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name><affiliation><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name><affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation></affiliation></author><author><name sortKey="Groop, Per Henrik" sort="Groop, Per Henrik" uniqKey="Groop P" first="Per-Henrik" last="Groop">Per-Henrik Groop</name><affiliation><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; per-henrik.groop@helsinki.fi.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of the American Society of Nephrology : JASN</title><idno type="eISSN">1533-3450</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Diabetes Mellitus, Type 1 (complications)</term><term>Diabetes Mellitus, Type 1 (genetics)</term><term>Diabetic Nephropathies (genetics)</term><term>Female</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Young Adult</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Diabetes Mellitus, Type 1</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Diabetes Mellitus, Type 1</term><term>Diabetic Nephropathies</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Female</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10(-5)) and the risk of type 2 diabetes (P=6.1×10(-4)) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10(-4)). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10(-6)), and pentose and glucuronate interconversions (P=3.0×10(-6)) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27647854</PMID><DateCreated><Year>2016</Year><Month>09</Month><Day>20</Day></DateCreated><DateCompleted><Year>2017</Year><Month>05</Month><Day>24</Day></DateCompleted><DateRevised><Year>2017</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1533-3450</ISSN><JournalIssue CitedMedium="Internet"><Volume>28</Volume><Issue>2</Issue><PubDate><Year>2017</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Journal of the American Society of Nephrology : JASN</Title><ISOAbbreviation>J. Am. Soc. Nephrol.</ISOAbbreviation></Journal><ArticleTitle>The Genetic Landscape of Renal Complications in Type 1 Diabetes.</ArticleTitle><Pagination><MedlinePgn>557-574</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1681/ASN.2016020231</ELocationID><Abstract><AbstractText>Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10(-5)) and the risk of type 2 diabetes (P=6.1×10(-4)) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10(-4)). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10(-6)), and pentose and glucuronate interconversions (P=3.0×10(-6)) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.</AbstractText><CopyrightInformation>Copyright © 2017 by the American Society of Nephrology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sandholm</LastName><ForeName>Niina</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van Zuydam</LastName><ForeName>Natalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Medical Research Institute, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ahlqvist</LastName><ForeName>Emma</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Juliusdottir</LastName><ForeName>Thorhildur</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deshmukh</LastName><ForeName>Harshal A</ForeName><Initials>HA</Initials><AffiliationInfo><Affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rayner</LastName><ForeName>N William</ForeName><Initials>NW</Initials><AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Di Camillo</LastName><ForeName>Barbara</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Forsblom</LastName><ForeName>Carol</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fadista</LastName><ForeName>Joao</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ziemek</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salem</LastName><ForeName>Rany M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Departments of Genetics, and.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Programs in Metabolism and Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Divisions of Endocrinology and Genetics, Boston Children's Hospital, Boston, Massachusetts.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hiraki</LastName><ForeName>Linda T</ForeName><Initials>LT</Initials><AffiliationInfo><Affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pezzolesi</LastName><ForeName>Marcus</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trégouët</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Sorbonne Universities, Pierre et Marie Curie University (UPMC) and National Institute for Health and Medical Research, Mixed Research Unit in Health (UMR_S) 1166, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute for Cardiometabolism and Nutrition, Genomics and pathophysiology of Cardiovascular diseases, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dahlström</LastName><ForeName>Emma</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Valo</LastName><ForeName>Erkka</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oskolkov</LastName><ForeName>Nikolay</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ladenvall</LastName><ForeName>Claes</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marcovecchio</LastName><ForeName>M Loredana</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>Department of Paediatrics, Institute of Metabolic Science, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cooper</LastName><ForeName>Jason</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sambo</LastName><ForeName>Francesco</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malovini</LastName><ForeName>Alberto</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratory of Informatics and Systems Engineering for Clinical Research, Scientific Institute for Research, Hospitalization and Health Care, IRCCS (Instituto di Ricovero e Cura a Carattere Scientifico); Salvatore Maugeri Foundation, Pavia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Manfrini</LastName><ForeName>Marco</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McKnight</LastName><ForeName>Amy Jayne</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lajer</LastName><ForeName>Maria</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harjutsalo</LastName><ForeName>Valma</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gordin</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Parkkonen</LastName><ForeName>Maija</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>FinnDiane Study Group, Jaakko Tuomilehto</CollectiveName></Author><Author ValidYN="Y"><LastName>Lyssenko</LastName><ForeName>Valeriya</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McKeigue</LastName><ForeName>Paul M</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rich</LastName><ForeName>Stephen S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brosnan</LastName><ForeName>Mary Julia</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Cardiovascular and Metabolic Diseases Research Unit, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fauman</LastName><ForeName>Eric</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge, Massachusetts.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bellazzi</LastName><ForeName>Riccardo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rossing</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Health, Aarhus University, Aarhus, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hadjadj</LastName><ForeName>Samy</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Endocrinology-Diabetology and Center of Clinical Investigation, Poitiers University Hospital, Poitiers, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute National pour la Santé et la Recherche Médicale, National Institute for Health and Medical Research, Center of Clinical Investigation 1402 and Unit 1082, Poitiers, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Krolewski</LastName><ForeName>Andrzej</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paterson</LastName><ForeName>Andrew D</ForeName><Initials>AD</Initials><AffiliationInfo><Affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>DCCT/EDIC Study Group, Jose C. Florez</CollectiveName></Author><Author ValidYN="Y"><LastName>Hirschhorn</LastName><ForeName>Joel N</ForeName><Initials>JN</Initials><AffiliationInfo><Affiliation>Departments of Genetics, and.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Programs in Metabolism and Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Divisions of Endocrinology and Genetics, Boston Children's Hospital, Boston, Massachusetts.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maxwell</LastName><ForeName>Alexander P</ForeName><Initials>AP</Initials><AffiliationInfo><Affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Regional Nephrology Unit, Belfast City Hospital, Belfast, United Kingdom; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>GENIE Consortium, David Dunger</CollectiveName></Author><Author ValidYN="Y"><LastName>Cobelli</LastName><ForeName>Claudio</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Colhoun</LastName><ForeName>Helen M</ForeName><Initials>HM</Initials><AffiliationInfo><Affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Groop</LastName><ForeName>Leif</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McCarthy</LastName><ForeName>Mark I</ForeName><Initials>MI</Initials><AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Groop</LastName><ForeName>Per-Henrik</ForeName><Initials>PH</Initials><AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; per-henrik.groop@helsinki.fi.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Baker IDI (International Diabetes Institute) Heart and Diabetes Institute, Melbourne, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>SUMMIT Consortium</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>U01 DK094176</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 DK081923</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 DK007260</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 DK105154</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U01 DK094157</GrantID><Acronym>DK</Acronym><Agency>NIDDK NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R00 HL122515</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>09</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Am Soc Nephrol</MedlineTA><NlmUniqueID>9013836</NlmUniqueID><ISSNLinking>1046-6673</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Nat Genet. 2010 May;42(5):441-7</RefSource><PMID Version="1">20418890</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Diabetes. 2010 Dec;59(12):3229-39</RefSource><PMID Version="1">20858683</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>QJM. 2013 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MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003922" MajorTopicYN="N">Diabetes Mellitus, Type 1</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003928" MajorTopicYN="N">Diabetic Nephropathies</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055106" MajorTopicYN="N">Genome-Wide Association Study</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">diabetic kidney disease</Keyword><Keyword MajorTopicYN="N">genetics and development</Keyword><Keyword MajorTopicYN="N">genome-wide association study</Keyword><Keyword MajorTopicYN="N">whole exome sequencing</Keyword></KeywordList><InvestigatorList><Investigator ValidYN="Y"><LastName>Sandholm</LastName><ForeName>N</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Van Zuydam</LastName><ForeName>N</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ahlqvist</LastName><ForeName>E</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Juliusdottir</LastName><ForeName>T</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Deshmukh</LastName><ForeName>H A</ForeName><Initials>HA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Di Camillo</LastName><ForeName>B</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Forsblom</LastName><ForeName>C</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fadista</LastName><ForeName>J</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ziemek</LastName><ForeName>D</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Salem</LastName><ForeName>R M</ForeName><Initials>RM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hiraki</LastName><ForeName>L T</ForeName><Initials>LT</Initials></Investigator><Investigator ValidYN="Y"><LastName>Pezzolesi</LastName><ForeName>M</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Trégouët</LastName><ForeName>D</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dahlström</LastName><ForeName>E</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Valo</LastName><ForeName>E</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Oskolkov</LastName><ForeName>N</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ladenvall</LastName><ForeName>C</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Marcovecchio</LastName><ForeName>M L</ForeName><Initials>ML</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cooper</LastName><ForeName>J</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Sambo</LastName><ForeName>F</ForeName><Initials>F</Initials></Investigator><Investigator ValidYN="Y"><LastName>Malovini</LastName><ForeName>A</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Manfrini</LastName><ForeName>M</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>McKnight</LastName><ForeName>A J</ForeName><Initials>AJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lajer</LastName><ForeName>M</ForeName><Initials>M</Initials><Suffix>5th</Suffix></Investigator><Investigator ValidYN="Y"><LastName>Gordin</LastName><ForeName>D</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Parkkonen</LastName><ForeName>M</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Tuomilehto</LastName><ForeName>J</ForeName><Initials>J</Initials><Suffix>5th</Suffix></Investigator><Investigator ValidYN="Y"><LastName>McKeigue</LastName><ForeName>P M</ForeName><Initials>PM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rich</LastName><ForeName>S S</ForeName><Initials>SS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Brosnan</LastName><ForeName>M J</ForeName><Initials>MJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fauman</LastName><ForeName>E</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bellazzi</LastName><ForeName>R</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rossing</LastName><ForeName>P</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hadjadj</LastName><ForeName>S</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Krolewski</LastName><ForeName>A</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Paterson</LastName><ForeName>A D</ForeName><Initials>AD</Initials></Investigator><Investigator ValidYN="Y"><LastName>Florez</LastName><ForeName>J C</ForeName><Initials>JC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hirschhorn</LastName><ForeName>J N</ForeName><Initials>JN</Initials></Investigator><Investigator ValidYN="Y"><LastName>Maxwell</LastName><ForeName>A P</ForeName><Initials>AP</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dunger</LastName><ForeName>D</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cobelli</LastName><ForeName>C</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Colhoun</LastName><ForeName>H M</ForeName><Initials>HM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Groop</LastName><ForeName>L</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>McCarthy</LastName><ForeName>M I</ForeName><Initials>MI</Initials></Investigator><Investigator ValidYN="Y"><LastName>Groop</LastName><ForeName>P-H</ForeName><Initials>PH</Initials></Investigator></InvestigatorList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>02</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>07</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2018</Year><Month>02</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>9</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>5</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>9</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27647854</ArticleId><ArticleId IdType="pii">ASN.2016020231</ArticleId><ArticleId IdType="doi">10.1681/ASN.2016020231</ArticleId><ArticleId IdType="pmc">PMC5280020</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour 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