The Genetic Landscape of Renal Complications in Type 1 Diabetes.
Identifieur interne : 000280 ( Main/Exploration ); précédent : 000279; suivant : 000281The Genetic Landscape of Renal Complications in Type 1 Diabetes.
Auteurs : Niina Sandholm [Finlande] ; Natalie Van Zuydam ; Emma Ahlqvist [Suède] ; Thorhildur Juliusdottir ; Harshal A. Deshmukh [Royaume-Uni] ; N William Rayner ; Barbara Di Camillo [Italie] ; Carol Forsblom [Finlande] ; Joao Fadista [Suède] ; Daniel Ziemek [Allemagne] ; Rany M. Salem ; Linda T. Hiraki [Canada] ; Marcus Pezzolesi [États-Unis] ; David Trégouët [France] ; Emma Dahlström [Finlande] ; Erkka Valo [Finlande] ; Nikolay Oskolkov [Suède] ; Claes Ladenvall [Suède] ; M Loredana Marcovecchio ; Jason Cooper [Royaume-Uni] ; Francesco Sambo [Italie] ; Alberto Malovini [Italie] ; Marco Manfrini [Italie] ; Amy Jayne Mcknight [Royaume-Uni] ; Maria Lajer [Danemark] ; Valma Harjutsalo [Finlande] ; Daniel Gordin [Finlande] ; Maija Parkkonen [Finlande] ; Valeriya Lyssenko [Suède] ; Paul M. Mckeigue [Royaume-Uni] ; Stephen S. Rich [États-Unis] ; Mary Julia Brosnan ; Eric Fauman [États-Unis] ; Riccardo Bellazzi [Italie] ; Peter Rossing [Danemark] ; Samy Hadjadj [France] ; Andrzej Krolewski [États-Unis] ; Andrew D. Paterson [Canada] ; Joel N. Hirschhorn ; Alexander P. Maxwell [Royaume-Uni] ; Claudio Cobelli [Italie] ; Helen M. Colhoun [Royaume-Uni] ; Leif Groop [Suède] ; Mark I. Mccarthy ; Per-Henrik Groop [Finlande]Source :
- Journal of the American Society of Nephrology : JASN [ 1533-3450 ] ; 2017.
Descripteurs français
- KwdFr :
- MESH :
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
Affiliations:
- Allemagne, Canada, Danemark, Finlande, France, Italie, Royaume-Uni, Suède, États-Unis
- Angleterre, Angleterre de l'Est, Berlin, Massachusetts, Nouvelle-Aquitaine, Poitou-Charentes, Virginie, Écosse, Île-de-France
- Berlin, Cambridge, Paris, Poitiers, Édimbourg
- Université d'Édimbourg, Université de Cambridge
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Salem</name><affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Pezzolesi, Marcus" sort="Pezzolesi, Marcus" uniqKey="Pezzolesi M" first="Marcus" last="Pezzolesi">Marcus Pezzolesi</name><affiliation wicri:level="2"><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Trégouët">David Trégouët</name><affiliation wicri:level="3"><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><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dahlstrom, Emma" sort="Dahlstrom, Emma" uniqKey="Dahlstrom E" first="Emma" last="Dahlström">Emma Dahlström</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Valo, Erkka" sort="Valo, Erkka" uniqKey="Valo E" first="Erkka" last="Valo">Erkka Valo</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Oskolkov, Nikolay" sort="Oskolkov, Nikolay" uniqKey="Oskolkov N" first="Nikolay" last="Oskolkov">Nikolay Oskolkov</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></affiliation></author><author><name sortKey="Ladenvall, Claes" sort="Ladenvall, Claes" uniqKey="Ladenvall C" first="Claes" last="Ladenvall">Claes Ladenvall</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Cooper, Jason" sort="Cooper, Jason" uniqKey="Cooper J" first="Jason" last="Cooper">Jason Cooper</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Sambo, Francesco" sort="Sambo, Francesco" uniqKey="Sambo F" first="Francesco" last="Sambo">Francesco Sambo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea><wicri:noRegion>Padova</wicri:noRegion></affiliation></author><author><name sortKey="Malovini, Alberto" sort="Malovini, Alberto" uniqKey="Malovini A" first="Alberto" last="Malovini">Alberto Malovini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Manfrini, Marco" sort="Manfrini, Marco" uniqKey="Manfrini M" first="Marco" last="Manfrini">Marco Manfrini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea><wicri:noRegion>Padova</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Lajer, Maria" sort="Lajer, Maria" uniqKey="Lajer M" first="Maria" last="Lajer">Maria Lajer</name><affiliation wicri:level="1"><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Diabetic Complications, Steno Diabetes Center, Gentofte</wicri:regionArea><wicri:noRegion>Gentofte</wicri:noRegion></affiliation></author><author><name sortKey="Harjutsalo, Valma" sort="Harjutsalo, Valma" uniqKey="Harjutsalo V" first="Valma" last="Harjutsalo">Valma Harjutsalo</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Gordin, Daniel" sort="Gordin, Daniel" uniqKey="Gordin D" first="Daniel" last="Gordin">Daniel Gordin</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Parkkonen, Maija" sort="Parkkonen, Maija" uniqKey="Parkkonen M" first="Maija" last="Parkkonen">Maija Parkkonen</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></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 wicri:level="4"><nlm:affiliation>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></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 wicri:level="2"><nlm:affiliation>Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Center for Public Health Genomics, University of Virginia, Charlottesville</wicri:cityArea></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><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Fauman, Eric" sort="Fauman, Eric" uniqKey="Fauman E" first="Eric" last="Fauman">Eric Fauman</name><affiliation wicri:level="2"><nlm:affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Bellazzi, Riccardo" sort="Bellazzi, Riccardo" uniqKey="Bellazzi R" first="Riccardo" last="Bellazzi">Riccardo Bellazzi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name><affiliation wicri:level="1"><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Diabetic Complications, Steno Diabetes Center, Gentofte</wicri:regionArea><wicri:noRegion>Gentofte</wicri:noRegion></affiliation></author><author><name sortKey="Hadjadj, Samy" sort="Hadjadj, Samy" uniqKey="Hadjadj S" first="Samy" last="Hadjadj">Samy Hadjadj</name><affiliation wicri:level="3"><nlm:affiliation>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Poitou-Charentes</region><settlement type="city">Poitiers</settlement></placeName></affiliation></author><author><name sortKey="Krolewski, Andrzej" sort="Krolewski, Andrzej" uniqKey="Krolewski A" first="Andrzej" last="Krolewski">Andrzej Krolewski</name><affiliation wicri:level="2"><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston</wicri:cityArea></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 wicri:level="1"><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Cobelli, Claudio" sort="Cobelli, Claudio" uniqKey="Cobelli C" first="Claudio" last="Cobelli">Claudio Cobelli</name><affiliation wicri:level="1"><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea><wicri:noRegion>Padova</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Population Health Sciences, University of Dundee, Dundee</wicri:regionArea><wicri:noRegion>Dundee</wicri:noRegion></affiliation></author><author><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; per-henrik.groop@helsinki.fi.</nlm:affiliation><country wicri:rule="url">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></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><idno type="wicri:Area/PubMed/Curation">001174</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001174</idno><idno type="wicri:Area/PubMed/Checkpoint">001174</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001174</idno><idno type="wicri:Area/Ncbi/Merge">003B64</idno><idno type="wicri:Area/Ncbi/Curation">003B64</idno><idno type="wicri:Area/Ncbi/Checkpoint">003B64</idno><idno type="wicri:Area/Main/Merge">000275</idno><idno type="wicri:Area/Main/Curation">000280</idno><idno type="wicri:Area/Main/Exploration">000280</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 wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Ahlqvist, Emma" sort="Ahlqvist, Emma" uniqKey="Ahlqvist E" first="Emma" last="Ahlqvist">Emma Ahlqvist</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Population Health Sciences, University of Dundee, Dundee</wicri:regionArea><wicri:noRegion>Dundee</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea><wicri:noRegion>Padova</wicri:noRegion></affiliation></author><author><name sortKey="Forsblom, Carol" sort="Forsblom, Carol" uniqKey="Forsblom C" first="Carol" last="Forsblom">Carol Forsblom</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Fadista, Joao" sort="Fadista, Joao" uniqKey="Fadista J" first="Joao" last="Fadista">Joao Fadista</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></affiliation></author><author><name sortKey="Ziemek, Daniel" sort="Ziemek, Daniel" uniqKey="Ziemek D" first="Daniel" last="Ziemek">Daniel Ziemek</name><affiliation wicri:level="3"><nlm:affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Berlin, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Computational Sciences, Pfizer Worldwide Research and Development, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></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><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Pezzolesi, Marcus" sort="Pezzolesi, Marcus" uniqKey="Pezzolesi M" first="Marcus" last="Pezzolesi">Marcus Pezzolesi</name><affiliation wicri:level="2"><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Trégouët">David Trégouët</name><affiliation wicri:level="3"><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><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dahlstrom, Emma" sort="Dahlstrom, Emma" uniqKey="Dahlstrom E" first="Emma" last="Dahlström">Emma Dahlström</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Valo, Erkka" sort="Valo, Erkka" uniqKey="Valo E" first="Erkka" last="Valo">Erkka Valo</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Oskolkov, Nikolay" sort="Oskolkov, Nikolay" uniqKey="Oskolkov N" first="Nikolay" last="Oskolkov">Nikolay Oskolkov</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></affiliation></author><author><name sortKey="Ladenvall, Claes" sort="Ladenvall, Claes" uniqKey="Ladenvall C" first="Claes" last="Ladenvall">Claes Ladenvall</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Cooper, Jason" sort="Cooper, Jason" uniqKey="Cooper J" first="Jason" last="Cooper">Jason Cooper</name><affiliation wicri:level="4"><nlm:affiliation>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Sambo, Francesco" sort="Sambo, Francesco" uniqKey="Sambo F" first="Francesco" last="Sambo">Francesco Sambo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea><wicri:noRegion>Padova</wicri:noRegion></affiliation></author><author><name sortKey="Malovini, Alberto" sort="Malovini, Alberto" uniqKey="Malovini A" first="Alberto" last="Malovini">Alberto Malovini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Manfrini, Marco" sort="Manfrini, Marco" uniqKey="Manfrini M" first="Marco" last="Manfrini">Marco Manfrini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea><wicri:noRegion>Padova</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Lajer, Maria" sort="Lajer, Maria" uniqKey="Lajer M" first="Maria" last="Lajer">Maria Lajer</name><affiliation wicri:level="1"><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Diabetic Complications, Steno Diabetes Center, Gentofte</wicri:regionArea><wicri:noRegion>Gentofte</wicri:noRegion></affiliation></author><author><name sortKey="Harjutsalo, Valma" sort="Harjutsalo, Valma" uniqKey="Harjutsalo V" first="Valma" last="Harjutsalo">Valma Harjutsalo</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Gordin, Daniel" sort="Gordin, Daniel" uniqKey="Gordin D" first="Daniel" last="Gordin">Daniel Gordin</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Parkkonen, Maija" sort="Parkkonen, Maija" uniqKey="Parkkonen M" first="Maija" last="Parkkonen">Maija Parkkonen</name><affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></affiliation></author><author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></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 wicri:level="4"><nlm:affiliation>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Edinburgh</wicri:regionArea><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region><settlement type="city">Édimbourg</settlement></placeName><orgName type="university">Université d'Édimbourg</orgName></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 wicri:level="2"><nlm:affiliation>Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Virginie</region></placeName><wicri:cityArea>Center for Public Health Genomics, University of Virginia, Charlottesville</wicri:cityArea></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><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Fauman, Eric" sort="Fauman, Eric" uniqKey="Fauman E" first="Eric" last="Fauman">Eric Fauman</name><affiliation wicri:level="2"><nlm:affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Bellazzi, Riccardo" sort="Bellazzi, Riccardo" uniqKey="Bellazzi R" first="Riccardo" last="Bellazzi">Riccardo Bellazzi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia</wicri:regionArea><wicri:noRegion>Pavia</wicri:noRegion></affiliation></author><author><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name><affiliation wicri:level="1"><nlm:affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Diabetic Complications, Steno Diabetes Center, Gentofte</wicri:regionArea><wicri:noRegion>Gentofte</wicri:noRegion></affiliation></author><author><name sortKey="Hadjadj, Samy" sort="Hadjadj, Samy" uniqKey="Hadjadj S" first="Samy" last="Hadjadj">Samy Hadjadj</name><affiliation wicri:level="3"><nlm:affiliation>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers</wicri:regionArea><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Poitou-Charentes</region><settlement type="city">Poitiers</settlement></placeName></affiliation></author><author><name sortKey="Krolewski, Andrzej" sort="Krolewski, Andrzej" uniqKey="Krolewski A" first="Andrzej" last="Krolewski">Andrzej Krolewski</name><affiliation wicri:level="2"><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston</wicri:cityArea></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 wicri:level="1"><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Cobelli, Claudio" sort="Cobelli, Claudio" uniqKey="Cobelli C" first="Claudio" last="Cobelli">Claudio Cobelli</name><affiliation wicri:level="1"><nlm:affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea><wicri:noRegion>Padova</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Population Health Sciences, University of Dundee, Dundee</wicri:regionArea><wicri:noRegion>Dundee</wicri:noRegion></affiliation></author><author><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea><wicri:noRegion>Malmö</wicri:noRegion></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><wicri:noCountry code="subField">and</wicri:noCountry></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 wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; per-henrik.groop@helsinki.fi.</nlm:affiliation><country wicri:rule="url">Finlande</country><wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea><wicri:noRegion>Helsinki</wicri:noRegion></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="KwdFr" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Diabète de type 1 ()</term><term>Diabète de type 1 (génétique)</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Néphropathies diabétiques (génétique)</term><term>Étude d'association pangénomique</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" qualifier="génétique" xml:lang="fr"><term>Diabète de type 1</term><term>Néphropathies diabétiques</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><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Diabète de type 1</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Mâle</term><term>Étude d'association pangénomique</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><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Danemark</li><li>Finlande</li><li>France</li><li>Italie</li><li>Royaume-Uni</li><li>Suède</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Berlin</li><li>Massachusetts</li><li>Nouvelle-Aquitaine</li><li>Poitou-Charentes</li><li>Virginie</li><li>Écosse</li><li>Île-de-France</li></region><settlement><li>Berlin</li><li>Cambridge</li><li>Paris</li><li>Poitiers</li><li>Édimbourg</li></settlement><orgName><li>Université d'Édimbourg</li><li>Université de Cambridge</li></orgName></list><tree><noCountry><name sortKey="Brosnan, Mary Julia" sort="Brosnan, Mary Julia" uniqKey="Brosnan M" first="Mary Julia" last="Brosnan">Mary Julia Brosnan</name><name sortKey="Hirschhorn, Joel N" sort="Hirschhorn, Joel N" uniqKey="Hirschhorn J" first="Joel N" last="Hirschhorn">Joel N. Hirschhorn</name><name sortKey="Juliusdottir, Thorhildur" sort="Juliusdottir, Thorhildur" uniqKey="Juliusdottir T" first="Thorhildur" last="Juliusdottir">Thorhildur Juliusdottir</name><name sortKey="Marcovecchio, M Loredana" sort="Marcovecchio, M Loredana" uniqKey="Marcovecchio M" first="M Loredana" last="Marcovecchio">M Loredana Marcovecchio</name><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name><name sortKey="Rayner, N William" sort="Rayner, N William" uniqKey="Rayner N" first="N William" last="Rayner">N William Rayner</name><name sortKey="Salem, Rany M" sort="Salem, Rany M" uniqKey="Salem R" first="Rany M" last="Salem">Rany M. Salem</name><name sortKey="Van Zuydam, Natalie" sort="Van Zuydam, Natalie" uniqKey="Van Zuydam N" first="Natalie" last="Van Zuydam">Natalie Van Zuydam</name></noCountry><country name="Finlande"><noRegion><name sortKey="Sandholm, Niina" sort="Sandholm, Niina" uniqKey="Sandholm N" first="Niina" last="Sandholm">Niina Sandholm</name></noRegion><name sortKey="Dahlstrom, Emma" sort="Dahlstrom, Emma" uniqKey="Dahlstrom E" first="Emma" last="Dahlström">Emma Dahlström</name><name sortKey="Forsblom, Carol" sort="Forsblom, Carol" uniqKey="Forsblom C" first="Carol" last="Forsblom">Carol Forsblom</name><name sortKey="Gordin, Daniel" sort="Gordin, Daniel" uniqKey="Gordin D" first="Daniel" last="Gordin">Daniel Gordin</name><name sortKey="Groop, Per Henrik" sort="Groop, Per Henrik" uniqKey="Groop P" first="Per-Henrik" last="Groop">Per-Henrik Groop</name><name sortKey="Harjutsalo, Valma" sort="Harjutsalo, Valma" uniqKey="Harjutsalo V" first="Valma" last="Harjutsalo">Valma Harjutsalo</name><name sortKey="Parkkonen, Maija" sort="Parkkonen, Maija" uniqKey="Parkkonen M" first="Maija" last="Parkkonen">Maija Parkkonen</name><name sortKey="Valo, Erkka" sort="Valo, Erkka" uniqKey="Valo E" first="Erkka" last="Valo">Erkka Valo</name></country><country name="Suède"><noRegion><name sortKey="Ahlqvist, Emma" sort="Ahlqvist, Emma" uniqKey="Ahlqvist E" first="Emma" last="Ahlqvist">Emma Ahlqvist</name></noRegion><name sortKey="Fadista, Joao" sort="Fadista, Joao" uniqKey="Fadista J" first="Joao" last="Fadista">Joao Fadista</name><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name><name sortKey="Ladenvall, Claes" sort="Ladenvall, Claes" uniqKey="Ladenvall C" first="Claes" last="Ladenvall">Claes Ladenvall</name><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name><name sortKey="Oskolkov, Nikolay" sort="Oskolkov, Nikolay" uniqKey="Oskolkov N" first="Nikolay" last="Oskolkov">Nikolay Oskolkov</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Deshmukh, Harshal A" sort="Deshmukh, Harshal A" uniqKey="Deshmukh H" first="Harshal A" last="Deshmukh">Harshal A. Deshmukh</name></noRegion><name sortKey="Colhoun, Helen M" sort="Colhoun, Helen M" uniqKey="Colhoun H" first="Helen M" last="Colhoun">Helen M. Colhoun</name><name sortKey="Cooper, Jason" sort="Cooper, Jason" uniqKey="Cooper J" first="Jason" last="Cooper">Jason Cooper</name><name sortKey="Maxwell, Alexander P" sort="Maxwell, Alexander P" uniqKey="Maxwell A" first="Alexander P" last="Maxwell">Alexander P. Maxwell</name><name sortKey="Mckeigue, Paul M" sort="Mckeigue, Paul M" uniqKey="Mckeigue P" first="Paul M" last="Mckeigue">Paul M. Mckeigue</name><name sortKey="Mcknight, Amy Jayne" sort="Mcknight, Amy Jayne" uniqKey="Mcknight A" first="Amy Jayne" last="Mcknight">Amy Jayne Mcknight</name></country><country name="Italie"><noRegion><name sortKey="Di Camillo, Barbara" sort="Di Camillo, Barbara" uniqKey="Di Camillo B" first="Barbara" last="Di Camillo">Barbara Di Camillo</name></noRegion><name sortKey="Bellazzi, Riccardo" sort="Bellazzi, Riccardo" uniqKey="Bellazzi R" first="Riccardo" last="Bellazzi">Riccardo Bellazzi</name><name sortKey="Cobelli, Claudio" sort="Cobelli, Claudio" uniqKey="Cobelli C" first="Claudio" last="Cobelli">Claudio Cobelli</name><name sortKey="Malovini, Alberto" sort="Malovini, Alberto" uniqKey="Malovini A" first="Alberto" last="Malovini">Alberto Malovini</name><name sortKey="Manfrini, Marco" sort="Manfrini, Marco" uniqKey="Manfrini M" first="Marco" last="Manfrini">Marco Manfrini</name><name sortKey="Sambo, Francesco" sort="Sambo, Francesco" uniqKey="Sambo F" first="Francesco" last="Sambo">Francesco Sambo</name></country><country name="Allemagne"><region name="Berlin"><name sortKey="Ziemek, Daniel" sort="Ziemek, Daniel" uniqKey="Ziemek D" first="Daniel" last="Ziemek">Daniel Ziemek</name></region></country><country name="Canada"><noRegion><name sortKey="Hiraki, Linda T" sort="Hiraki, Linda T" uniqKey="Hiraki L" first="Linda T" last="Hiraki">Linda T. Hiraki</name></noRegion><name sortKey="Paterson, Andrew D" sort="Paterson, Andrew D" uniqKey="Paterson A" first="Andrew D" last="Paterson">Andrew D. Paterson</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Pezzolesi, Marcus" sort="Pezzolesi, Marcus" uniqKey="Pezzolesi M" first="Marcus" last="Pezzolesi">Marcus Pezzolesi</name></region><name sortKey="Fauman, Eric" sort="Fauman, Eric" uniqKey="Fauman E" first="Eric" last="Fauman">Eric Fauman</name><name sortKey="Krolewski, Andrzej" sort="Krolewski, Andrzej" uniqKey="Krolewski A" first="Andrzej" last="Krolewski">Andrzej Krolewski</name><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S" last="Rich">Stephen S. Rich</name></country><country name="France"><region name="Île-de-France"><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Trégouët">David Trégouët</name></region><name sortKey="Hadjadj, Samy" sort="Hadjadj, Samy" uniqKey="Hadjadj S" first="Samy" last="Hadjadj">Samy Hadjadj</name></country><country name="Danemark"><noRegion><name sortKey="Lajer, Maria" sort="Lajer, Maria" uniqKey="Lajer M" first="Maria" last="Lajer">Maria Lajer</name></noRegion><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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