The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Leif Groop

Leif Groop

Principal investigator

Leif Groop

The genetic landscape of renal complications in type 1 diabetes

Author

  • 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
  • Jaakko Tuomilehto
  • Valeriya Lyssenko
  • Paul M. McKeigue
  • Stephen S. Rich
  • Mary Julia Brosnan
  • Eric Fauman
  • Riccardo Bellazzi
  • Peter Rossing
  • Samy Hadjadj
  • Andrzej Krolewski
  • Andrew D. Paterson
  • Jose C. Florez
  • Joel N. Hirschhorn
  • Alexander P. Maxwell
  • David Dunger
  • Claudio Cobelli
  • Helen M. Colhoun
  • Leif Groop
  • Mark I. McCarthy
  • Per Henrik Groop

Summary, in English

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=6.4310-3). 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 associatedvariants.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=2.2310-5) and the risk of type 2 diabetes (P=6.1310-4) associated with the risk of diabetic kidney disease.Wealso found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1310-4). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0310-6), and pentose and glucuronate interconversions (P=3.0310-6) 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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Department of Clinical Sciences, Malmö
  • EpiHealth: Epidemiology for Health

Publishing year

2017

Language

English

Pages

557-574

Publication/Series

Journal of the American Society of Nephrology

Volume

28

Issue

2

Document type

Journal article

Publisher

American Society of Nephrology

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1046-6673