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Olle Melander

Principal investigator

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A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

Author

  • Natalie R van Zuydam
  • Emma Ahlqvist
  • Claes Ladenvall
  • Peter Almgren
  • Christina-Alexandra Schulz
  • Marju Orho-Melander
  • Olle Melander
  • Valeriya Lyssenko
  • Tiinamaija Tuomi
  • Leif C Groop
  • Mark I McCarthy

Other contributions

  • Jasmina Kravic

Summary, in English

Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10-8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes - Cardiovascular Disease
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • Diabetic Complications

Publishing year

2018-07

Language

English

Pages

1414-1427

Publication/Series

Diabetes

Volume

67

Issue

7

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Medical Genetics
  • Endocrinology and Diabetes

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Diabetes Mellitus, Type 2/complications
  • Diabetic Nephropathies/epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Kidney Failure, Chronic/complications
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Renal Insufficiency, Chronic/complications

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension
  • Diabetic Complications

ISBN/ISSN/Other

  • ISSN: 1939-327X