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van Zuydam, N.R.* ; Ahlqvist, E.* ; Sandholm, N.* ; Deshmukh, H.* ; Rayner, N.W.* ; Ladenvall, C.* ; Ziemek, D.* ; Fauman, E.* ; Robertson, N.R.* ; McKeigue, P.M.* ; Valo, E.* ; Forsblom, C.* ; Harjutsalo, V.* ; Perna, A.* ; Rurali, E.* ; Marcovecchio, M.L.* ; Igo, R.P.* ; Salem, R.M.* ; Perico, N.* ; Lajer, M.* ; Käräjämäki, A.* ; Imamura, M.* ; Kubo, M.* ; Takahashi, A.* ; Sim, X.* ; Liu, J.* ; van Dam, R.M.* ; Jiang, G.* ; Tam, C.H.T.* ; Luk, A.O.Y.* ; Lee, H.M.* ; Lim, C.K.P.* ; Szeto, C.C.* ; So, W.Y.* ; Chan, J.C.N.* ; Ang, S.F.* ; Dorajoo, R.* ; Wang, L.* ; Clara, T.S.H.* ; McKnight, A.J.* ; Duffy, S.* ; Pezzolesi, M.G.* ; Marre, M.* ; Gyorgy, B.* ; Hadjadj, S.* ; Hiraki, L.T.* ; Ahluwalia, T.S.* ; Almgren, P.* ; Schulz, C.A.* ; Orho-Melander, M.* ; Linneberg, A.* ; Christensen, C.* ; Witte, D.R.* ; Grarup, N.* ; Brandslund, I.* ; Melander, O.* ; Paterson, A.D.* ; Tregouet, D.* ; Maxwell, A.P.* ; Lim, S.C.* ; Ma, R.C.W.* ; Tai, E.S.* ; Maeda, S.* ; Lyssenko, V.* ; Tuomi, T.* ; Krolewski, A.S.* ; Rich, S.S.* ; Hirschhorn, J.N.* ; Florez, J.C* ; Dunger, D.B.* ; Pedersen, O.* ; Hansen, T.* ; Rossing, P.* ; Remuzzi, G.* ; SUMMIT Investigators (Thorand, B. ; Gieger, C. ; Grallert, H. ; Ludwig, T. ; Nitz, B. ; Wang-Sattler, R. ; Zierer, A.)

A genome-wide association study of diabetic kidney disease in subjects with type 2 diabetes.

Diabetes 67, 1414-1427 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 (rs9942471, = 4.5 × 10) 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 and , 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 67, Issue: 7, Pages: 1414-1427 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)