A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.
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Authors
Ahlqvist, Emma
Deshmukh, Harshal
Rayner, N William
Abdalla, Moustafa
Ladenvall, Claes
Ziemek, Daniel
Fauman, Eric
Robertson, Neil R
McKeigue, Paul M
Valo, Erkka
Forsblom, Carol
Harjutsalo, Valma
Finnish Diabetic Nephropathy Study (FinnDiane)
Perna, Annalisa
Rurali, Erica
Igo, Robert P
Salem, Rany M
Perico, Norberto
Lajer, Maria
Käräjämäki, Annemari
Imamura, Minako
Kubo, Michiaki
Takahashi, Atsushi
Sim, Xueling
Liu, Jianjun
van Dam, Rob M
Jiang, Guozhi
Tam, Claudia HT
Luk, Andrea OY
Lee, Heung Man
Lim, Cadmon KP
Szeto, Cheuk Chun
So, Wing Yee
Chan, Juliana CN
Hong Kong Diabetes Registry Theme-based Research Scheme Project Group
Ang, Su Fen
Dorajoo, Rajkumar
Wang, Ling
Clara, Tan Si Hua
McKnight, Amy-Jayne
Duffy, Seamus
Warren 3 and Genetics of Kidneys in Diabetes (GoKinD) Study Group
Pezzolesi, Marcus G
GENIE (GEnetics of Nephropathy an International Effort) Consortium
Marre, Michel
Gyorgy, Beata
Hadjadj, Samy
Hiraki, Linda T
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group
Ahluwalia, Tarunveer S
Almgren, Peter
Schulz, Christina-Alexandra
Orho-Melander, Marju
Linneberg, Allan
Christensen, Cramer
Witte, Daniel R
Grarup, Niels
Brandslund, Ivan
Melander, Olle
Paterson, Andrew D
Tregouet, David
Maxwell, Alexander P
Lim, Su Chi
Ma, Ronald CW
Tai, E Shyong
Maeda, Shiro
Lyssenko, Valeriya
Tuomi, Tiinamaija
Krolewski, Andrzej S
Rich, Stephen S
Hirschhorn, Joel N
Florez, Jose C
Pedersen, Oluf
Hansen, Torben
Rossing, Peter
Remuzzi, Giuseppe
SUrrogate markers for Micro- and Macrovascular hard endpoints for Innovative diabetes Tools (SUMMIT) Consortium
Brosnan, Mary Julia
Palmer, Colin NA
Groop, Leif C
McCarthy, Mark I
Publication Date
2018-07Journal Title
Diabetes
ISSN
0012-1797
Publisher
American Diabetes Association
Volume
67
Issue
7
Pages
1414-1427
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
van Zuydam, N. R., Ahlqvist, E., Sandholm, N., Deshmukh, H., Rayner, N. W., Abdalla, M., Ladenvall, C., et al. (2018). A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.. Diabetes, 67 (7), 1414-1427. https://doi.org/10.2337/db17-0914
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
Identifiers
External DOI: https://doi.org/10.2337/db17-0914
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283546
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