A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

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van Zuydam , N R , Ahlqvist , E , Sandholm , N , Deshmukh , H , Rayner , N W , Abdalla , M , 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 , Karajamak , 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 , Tuomi , T , Groop , P-H & Groop , L C 2018 , ' A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes ' , Diabetes , vol. 67 , no. 7 , pp. 1414-1427 . https://doi.org/10.2337/db17-0914

Title: A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
Author: 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; Karajamak, 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.; Tuomi, Tiinamaija; Groop, Per-Henrik; Groop, Leif C.
Contributor organization: Clinicum
Diabetes and Obesity Research Program
Research Programs Unit
Nefrologian yksikkö
Department of Medicine
Institute for Molecular Medicine Finland
Tiinamaija Tuomi Research Group
Endokrinologian yksikkö
Per Henrik Groop / Principal Investigator
Leif Groop Research Group
HUS Abdominal Center
HUS Internal Medicine and Rehabilitation
Date: 2018-07
Language: eng
Number of pages: 14
Belongs to series: Diabetes
ISSN: 0012-1797
DOI: https://doi.org/10.2337/db17-0914
URI: http://hdl.handle.net/10138/303851
Abstract: dentification 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 x 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.
Subject: STAGE RENAL-DISEASE
INSULIN-RESISTANCE
SUSCEPTIBILITY GENES
BIOLOGICAL PATHWAYS
FAT DISTRIBUTION
NEPHROPATHY
LOCI
METAANALYSIS
RISK
OBESITY
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion


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