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

Diabetes
Authors
Keywords
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 (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.

Year of Publication
2018
Journal
Diabetes
Volume
67
Issue
7
Pages
1414-1427
Date Published
2018 07
ISSN
1939-327X
DOI
10.2337/db17-0914
PubMed ID
29703844
PubMed Central ID
PMC6014557
Links
Grant list
098381 / WT_ / Wellcome Trust / United Kingdom
MC_PC_15025 / MRC_ / Medical Research Council / United Kingdom
084726/Z/08/Z / WT_ / Wellcome Trust / United Kingdom
P30 DK036836 / DK / NIDDK NIH HHS / United States
084727/Z/08/Z / WT_ / Wellcome Trust / United Kingdom
090532 / WT_ / Wellcome Trust / United Kingdom
R01 DK105154 / DK / NIDDK NIH HHS / United States
WT_ / Wellcome Trust / United Kingdom
R00 HL122515 / HL / NHLBI NIH HHS / United States
072960/Z/03/Z / WT_ / Wellcome Trust / United Kingdom
085475/Z/08/Z / WT_ / Wellcome Trust / United Kingdom
R01 MH101814 / MH / NIMH NIH HHS / United States
P30 DK017047 / DK / NIDDK NIH HHS / United States
085475/B/08/Z / WT_ / Wellcome Trust / United Kingdom
106310 / WT_ / Wellcome Trust / United Kingdom