Journal
DIABETES
Volume 67, Issue 7, Pages 1414-1427Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db17-0914
Keywords
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Categories
Funding
- European Union's Seventh Framework Program (FP7) for the Innovative Medicine Initiative [IMI/115006]
- Academy of Finland [263401, 267882]
- Association Diabete Risque Vasculaire in Paris
- Agency for Science, Technology and Research (A* STAR) in Singapore
- Albert Pahlsson Foundation
- Diabetesfonden
- Alexandra Health [SIGII/08005, SIGII/11001, SIG/11029, SIG/12024, SIG II/15205]
- Chinese University of Hong Kong Focused Investment Scheme
- Danish Diabetes Academy
- DOLOrisk (European Union's Horizon research and innovation program) [633491]
- European Research Council [269045-GENE TARGET T2D, 649021]
- Ernhold Lundstrom
- Finska Lakaresallskapet
- Folkhalsan Research Foundation
- French Ministry of Health
- Heart Foundation of Jakobstad region
- Helsinki University Central Hospital Research Funds
- Hong Kong Food and Health Bureau [01120796]
- Hong Kong Foundation for Research and Development in Diabetes
- Hong Kong Government Research Grant Committee and Innovation and Technology Grant Committee
- Hong Kong Research Grants Council Theme-based Research Scheme [T12-402/13N]
- Japan Agency for Medical Research and Development
- JDRF [17-2012-542, 17-2013-7, 2-SRA-2014-276-Q-R, 17-2013-9]
- Knut and Alice Wallenberg Foundation
- Leading Project of Ministry of Education, Culture, Sports, Science and Technology in Japan
- Liao Wun Yuk Memorial Fund
- Linneus Foundation for the Lund University Diabetes Center
- Liv och Halsa Foundation
- Ministry of Education, Culture, Sports, Science and Technology of the Japanese government
- National Institute for Health Research Cambridge Biomedical Research Centre
- National Medical Research Council in Singapore [CIRG13nov045]
- Natural Sciences and Engineering Research Council of Canada
- National Health Services Tayside
- National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK105154]
- National Institutes for Health [R01-MH101814]
- Novo Nordisk Foundation [NNF14SA0003, NNF15CC0018486]
- Pahlsson Foundation
- Region Skane
- Rhodes Trust
- Signe and Ane Gyllenberg Foundation
- Sigrid Juselius Foundation
- Skane University Hospital
- Societe Francophone du Diabete
- Swedish Diabetes Foundation
- Swedish Heart and Lung Foundation
- Swedish Research Council
- Turku University Hospital Research Funds
- University of Dundee
- Vasa Hospital District
- Wellcome [072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z, 098381, 090532, 106310]
- Wilhelm and Else Stockmann Foundation
- Wellcome Trust [085475/Z/08/Z, 084726/Z/08/Z, 085475/B/08/Z] Funding Source: Wellcome Trust
- MRC [MC_PC_15025] Funding Source: UKRI
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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 x 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.
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