Related Papers
Genome-wide association study of diabetic kidney disease highlights biology involved in renal basem*nt membrane collagen
Henrik Falhammar
Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions based on albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basem*nt membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of DKD, including albuminuria and end-stage renal disease. Three other loci are in or near genes with known or suggestive involvement in DKD (BMP7) or renal biology (COLEC11 and DDR1). The 16 DKD-associated loci provide novel insights into the pathogenesis of DKD, identifying potential bio...
Diabetes
A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
2018 •
Juliana Chan
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 diabetic subjects (and 18,582 DKD cases).Analysis of specific DKD phenotypes identified a novel signal near (rs9942471, =4.5×10) associated with 'microalbuminuria' in European T2D cases. However, no replication of this signal was observed in Asian subjects with T2D, or in the equivalent T1D analysis. Th...
Journal of the American Society of Nephrology : JASN
The Genetic Landscape of Renal Complications in Type 1 Diabetes
2016 •
Francesco Sambo
Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body...
PLoS Genetics
New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes
2012 •
Cristian Serafinceanu
Journal of the American Society of Nephrology : JASN
Genetics of Diabetic Kidney Disease-From the Worst of Nightmares to the Light of Dawn?
2017 •
Mark Cooper
PLoS genetics
Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)
2015 •
Sudha Iyengar
Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysi...
Características del periodo postquirúrgico inmediato y mediato de trauma abdominal en el Hospital San Juan de Lurigancho durante el periodo 2012 – 2014
2015 •
edwin apaza
Nidogen-1 Could Play a Role in Diabetic Kidney Disease Development: A Genome Wide Association Meta-analysis
Ali Torkamani
Background:Diabetic kidney disease (DKD) affects about 40% of patients with diabetes. It is uncurable and usually lead to end-stage renal disease (ESRD). The pathogenesis of DKD is still not fully understood and the genetics of DKD have not yet been extensively studied.In this study we investigate the genetic basis of DKD in type 2 diabetes (T2D) to provide more insights into the pathogenesis of the disease.Results:Using the data provided by the UK Biobank (UKBB), we performed a DKD genome-wide association study (GWAS) in 13,123 individuals with T2D as well as two creatinine estimated glomerular filtration rate (eGFR) GWA studies; one in 28,136 individuals with T2D and the other in 339,080 non-diabetic individuals. We also conducted a DKD GWAS meta-analysis combining our results with those published by the SUMMIT consortium.We confirm two loci previously reported to be associated with chronic kidney disease (CKD) and eGFR in T2D. The UMOD-PDILT locus is associated with DKD (P = 1.08...
Human Genomics
Nidogen-1 could play a role in diabetic kidney disease development in type 2 diabetes: a genome-wide association meta-analysis
Ali Torkamani
Background Diabetic kidney disease (DKD) affects about 40% of patients with diabetes. It is incurable and usually leads to end-stage renal disease (ESRD). The pathogenesis of DKD is still not fully understood, and the genetics of DKD have not yet been extensively studied. In this study, we investigate the genetic basis of DKD in type 2 diabetes (T2D) to provide more insights into the pathogenesis of the disease. Results Using the data provided by the UK Biobank (UKBB), we performed a DKD genome-wide association study (GWAS) in 13,123 individuals with T2D as well as two creatinine estimated glomerular filtration rate (eGFR) GWA studies: one in 26,786 individuals with T2D and the other in 339,080 non-diabetic individuals. We also conducted a DKD GWAS meta-analysis combining our results with those published by the surrogate markers for micro- and macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) consortium. We confirm two loci previously reported to be associated wit...
Journal of Personalized Medicine
Association of UBE3C Variants with Reduced Kidney Function in Patients with Diabetic Kidney Disease
Mai-szu Wu
Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM) and the most common variant of end-stage renal disease (ESRD) globally. The economic burden of ESRD treatment with dialysis is substantial. The incidence and prevalence of ESRD in Taiwan remain the highest worldwide. Therefore, identifying genetic factors affecting kidney function would have valuable clinical implications. We performed microarray experiments and identified that ubiquitin protein ligase E3C (UBE3C) is differentially expressed in two DKD patient groups with extreme (low and high) urine protein-to-creatinine ratios. A follow-up genotyping study was performed in a larger group to investigate any specific variants of UBE3C associated with DKD. A total of 263 patients were included in the study, comprising 172 patients with DKD and 91 control subjects (patients with DM without chronic kidney disease (CKD)). Two UBE3C variants (rs3802129(AA) and rs7807(CC))...
