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New loci associated with kidney function and chronic kidney disease

Anna Köttgen, +137 more
- 01 May 2010 - 
- Vol. 42, Iss: 5, pp 376-384
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TLDR
The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry to identify new susceptibility loci for reduced renal function as estimated by serum creatinine, serum cystatin c and CKD.
Abstract
Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.

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Journal ArticleDOI

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Georg Ehret, +391 more
- 06 Oct 2011 - 
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Journal ArticleDOI

Systematic identification of trans eQTLs as putative drivers of known disease associations

Harm-Jan Westra, +60 more
- 01 Oct 2013 - 
TL;DR: Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.
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A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Lars G. Fritsche, +185 more
- 01 Feb 2016 - 
TL;DR: The results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
References
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Journal ArticleDOI

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI

A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation

TL;DR: The purpose of this study was to develop an equation from MDRD Study data that could improve the prediction of GFR from serum creatinine concentration, and major clinical decisions in general medicine, geriatrics, and oncology are made by using the Cockcroft-Gault formula and other formulas to predict the level of renal function.
Journal Article

K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification

TL;DR: In the early 1990s, the National Kidney Foundation (K/DOQI) developed a set of clinical practice guidelines to define chronic kidney disease and to classify stages in the progression of kidney disease.
Journal ArticleDOI

Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

TL;DR: The longitudinal glomerular filtration rate was estimated among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation.
Journal ArticleDOI

Principal components analysis corrects for stratification in genome-wide association studies

TL;DR: This work describes a method that enables explicit detection and correction of population stratification on a genome-wide scale and uses principal components analysis to explicitly model ancestry differences between cases and controls.
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