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Title: A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes
Authors: van Zuydam, Natalie R.
Ahlqvist, Emma
Sandholm, Niina
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
Perna, Annalisa
Rurali, Erica
Marcovecchio, M Loredana
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 H. T.
Luk, Andrea O. Y.
Lee, Heung Man
Lim, Cadmon K. P.
Szeto, Cheuk Chun
So, Wing Yee
Chan, Juliana C. N.
Ang, Su Fen
Dorajoo, Rajkumar
Wang, Ling
Clara, Tan Si Hua
McKnight, Amy-Jayne
Duffy, Seamus
Pezzolesi, Marcus G.
Marre, Michel
Gyorgy, Beata
Hadjadj, Samy
Hiraki, Linda T.
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 C. W.
Tai, E. Shyong
Maeda, Shiro
Lyssenko, Valeriya
Tuomi, Tiinamaija
Krolewski, Andrzej S.
Rich, Stephen S.
Hirschhorn, Joel N.
Florez, Jose C.
Dunger, David
Pedersen, Oluf
Hansen, Torben
Rossing, Peter
Remuzzi, Giuseppe
Brosnan, Mary Julia
Palmer, Colin N. A.
Groop, Per-Henrik
Colhoun, Helen M.
Groop, Leif C.
McCarthy, Mark I.
Keywords: Science::Medicine
Issue Date: 2018
Source: van Zuydam, N. R., Ahlqvist, E., Sandholm, N., Deshmukh, H., Rayner, N. W., Abdalla, M., . . . McCarthy, M. I. (2018). A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes. Diabetes, 67(7), 1414-1427. doi:10.2337/db17-0914
Journal: Diabetes
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.
ISSN: 0012-1797
DOI: 10.2337/db17-0914
Rights: © 2018 The American Diabetes Association. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:LKCMedicine Journal Articles

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