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Type: Journal article
Title: A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes
Author: Van Zuydam, N.
Ahlqvist, E.
Sandholm, N.
Deshmukh, H.
William Rayner, N.
Abdalla, M.
Ladenvall, C.
Ziemek, D.
Fauman, E.
Robertson, N.
McKeigue, P.
Valo, E.
Forsblom, C.
Harjutsalo, V.
Perna, A.
Rurali, E.
Loredana Marcovecchio, M.
Igo, R.
Salem, R.
Perico, N.
et al.
Citation: Diabetes, 2018; 67(7):1414-1427
Publisher: American Diabetes Association
Issue Date: 2018
ISSN: 0012-1797
Statement of
Natalie R. van Zuydam, Emma Ahlqvist, Niina Sandholm, Harshal Deshmukh, N. William Rayner ... Ville-Petteri Makinen ... et al.
Abstract: 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.
Keywords: Finnish Diabetic Nephropathy Study (FinnDiane); Hong Kong Diabetes Registry Theme-based Research Scheme Project Group; Warren 3 and Genetics of Kidneys in Diabetes (GoKinD) Study Group; GENIE (GEnetics of Nephropathy an International Effort) Consortium; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group; SUrrogate markers for Micro- and Macrovascular hard endpoints for Innovative diabetes Tools (SUMMIT) Consortium; Humans; Diabetic Nephropathies; Kidney Failure, Chronic; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Case-Control Studies; Polymorphism, Single Nucleotide; Adult; Aged; Aged, 80 and over; Middle Aged; Female; Male; Renal Insufficiency, Chronic; Genome-Wide Association Study
Rights: Copyright status unknown
RMID: 0030109990
DOI: 10.2337/db17-0914
Appears in Collections:Medicine publications

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