دورية أكاديمية
The Genetic Landscape of Renal Complications in Type 1 Diabetes
| العنوان: | The Genetic Landscape of Renal Complications in Type 1 Diabetes |
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| المؤلفون: | Sandholm, Niina, Van Zuydam, Natalie, Ahlqvist, Emma, Juliusdottir, Thorhildur, Deshmukh, Harshal A, Rayner, N. William, Di Camillo, Barbara, Forsblom, Carol, Fadista, Joao, Ziemek, Daniel, Salem, Rany M, Hiraki, Linda T, Pezzolesi, Marcus, Trégouët, David, Dahlström, Emma, Valo, Erkka, Oskolkov, Nikolay, Ladenvall, Claes, Marcovecchio, M. Loredana, Cooper, Jason, Sambo, Francesco, Manfrini, Marco, Mcknight, Amy Jayne, Lajer, Maria, Harjutsalo, Valma, Gordin, Daniel, Parkkonen, Maija, Lyssenko, Valeriya, Mckeigue, Paul M, Rich, Stephen S, Brosnan, Mary Julia, Fauman, Eric, Rossing, Peter, Hadjadj, Samy, Krolewski, Andrzej, Paterson, Andrew D, Hirschhorn, Joel N, Maxwell, Alexander P, Cobelli, Claudio, Colhoun, Helen M, Groop, Leif, Mccarthy, Mark I, Groop, Per Henrik, MALOVINI, ALBERTO LUIGI, BELLAZZI, RICCARDO |
| المساهمون: | Sandholm, Niina, Van Zuydam, Natalie, Ahlqvist, Emma, Juliusdottir, Thorhildur, Deshmukh, Harshal A, Rayner, N. William, Di Camillo, Barbara, Forsblom, Carol, Fadista, Joao, Ziemek, Daniel, Salem, Rany M, Hiraki, Linda T, Pezzolesi, Marcu, Trégouët, David, Dahlström, Emma, Valo, Erkka, Oskolkov, Nikolay, Ladenvall, Clae, Marcovecchio, M. Loredana, Cooper, Jason, Sambo, Francesco, Malovini, ALBERTO LUIGI, Manfrini, Marco, Mcknight, Amy Jayne, Lajer, Maria, Harjutsalo, Valma, Gordin, Daniel, Parkkonen, Maija, Lyssenko, Valeriya, Mckeigue, Paul M, Rich, Stephen S, Brosnan, Mary Julia, Fauman, Eric, Bellazzi, Riccardo, Rossing, Peter, Hadjadj, Samy, Krolewski, Andrzej, Paterson, Andrew D, Hirschhorn, Joel N, Maxwell, Alexander P, Cobelli, Claudio, Colhoun, Helen M, Groop, Leif, Mccarthy, Mark I, Groop, Per Henrik |
| سنة النشر: | 2017 |
| المجموعة: | IRIS UNIPV (Università degli studi di Pavia) |
| مصطلحات موضوعية: | diabetic kidney disease, genetics and development, genome-wide association study, whole exome sequencing |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27647854; info:eu-repo/semantics/altIdentifier/wos/WOS:000393017600019; volume:28; issue:2; firstpage:557-574; lastpage:574; journal:JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; http://hdl.handle.net/11571/1179348Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85021404855 |
| DOI: | 10.1681/ASN.2016020231 |
| الإتاحة: | https://doi.org/10.1681/ASN.2016020231Test http://hdl.handle.net/11571/1179348Test |
| رقم الانضمام: | edsbas.D556F979 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1681/ASN.2016020231 |
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