| Literature DB >> 29703844 |
Natalie R van Zuydam1,2, Emma Ahlqvist3, Niina Sandholm4,5,6, Harshal Deshmukh7, N William Rayner8,2,9, Moustafa Abdalla8,2,10, Claes Ladenvall3, Daniel Ziemek11, Eric Fauman12, Neil R Robertson8,2, Paul M McKeigue13, Erkka Valo4,5,6, Carol Forsblom4,5,6, Valma Harjutsalo4,5,6,14, Annalisa Perna15, Erica Rurali15, M Loredana Marcovecchio16, Robert P Igo17, Rany M Salem18, Norberto Perico15, Maria Lajer19, Annemari Käräjämäki20,21, Minako Imamura22,23,24, Michiaki Kubo24, Atsushi Takahashi25,26, Xueling Sim27, Jianjun Liu27,28,29, Rob M van Dam27, Guozhi Jiang30, Claudia H T Tam30, Andrea O Y Luk30,31,32, Heung Man Lee30,31,32,33, Cadmon K P Lim30, Cheuk Chun Szeto30, Wing Yee So30, Juliana C N Chan30,31,32, Su Fen Ang34, Rajkumar Dorajoo28, Ling Wang28, Tan Si Hua Clara34, Amy-Jayne McKnight35, Seamus Duffy35, Marcus G Pezzolesi36, Michel Marre37, Beata Gyorgy37, Samy Hadjadj38,39,40, Linda T Hiraki41, Tarunveer S Ahluwalia19,42, Peter Almgren43, Christina-Alexandra Schulz43, Marju Orho-Melander43, Allan Linneberg44,45,46, Cramer Christensen47, Daniel R Witte48,49, Niels Grarup42, Ivan Brandslund50,51, Olle Melander52, Andrew D Paterson41, David Tregouet37, Alexander P Maxwell35, Su Chi Lim53,54,55, Ronald C W Ma30,31,32,33, E Shyong Tai27,54,56, Shiro Maeda22,23,24, Valeriya Lyssenko3,57, Tiinamaija Tuomi4,6,58,59, Andrzej S Krolewski60, Stephen S Rich61, Joel N Hirschhorn62,63,64, Jose C Florez63,65,66, David Dunger16,67, Oluf Pedersen42, Torben Hansen42,68, Peter Rossing19,42, Giuseppe Remuzzi15,69,70, Mary Julia Brosnan71, Colin N A Palmer72, Per-Henrik Groop4,5,6,73, Helen M Colhoun74, Leif C Groop3,59, Mark I McCarthy8,2,75.
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.Entities:
Mesh：
Year: 2018 PMID： 29703844 PMCID： PMC6014557 DOI： 10.2337/db17-0914
Source DB: PubMed Journal: Diabetes ISSN： 0012-1797 Impact factor: 9.461