Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide association studies in pediatric chronic kidney disease.

ABSTRACT: The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression.

SUBMITTER: Gupta J

PROVIDER: S-EPMC5287054 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genome-wide association studies in pediatric chronic kidney disease.

Gupta Jayanta J Kanetsky Peter A PA Wuttke Matthias M Köttgen Anna A Schaefer Franz F Wong Craig S CS

Pediatric nephrology (Berlin, Germany) 20151021 8

The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementa ...[more]

PMID: 26490952

Similar Datasets

Genome-wide association studies reconstructing chronic kidney disease.

Project description:Chronic kidney disease (CKD) is a major health problem with an increasing epidemiological burden, and is the 16th leading cause of years of life lost worldwide. It is estimated that more than 10% of the population have a variable stage of CKD, while about 850 million people worldwide are affected. Nevertheless, public awareness remains low, clinical access is inappropriate in many circumstances and medication is still ineffective due to the lack of clear therapeutic targets. One of the main issues that drives these problems is the fact that CKD remains a clinical entity with significant causal ambiguity. Beyond diabetes mellitus and hypertension, which are the two major causes of kidney disease, there are still many gray areas in the diagnostic context of CKD. Genetics nowadays emerges as a promising field in nephrology. The role of genetic factors in CKD's causes and predisposition is well documented and thousands of genetic variants are well established to contribute to the high burden of disease. Next-generation sequencing is increasingly revealing old and new rare variants that cause Mendelian forms of chronic nephropathy while genome-wide association studies (GWAS) uncover common variants associated with CKD-defining traits in the general population. In this article we review how GWAS has revolutionized-and continues to revolutionize-the old concept of CKD. Furthermore, we present how the investigation of common genetic variants with previously unknown kidney significance has begun to expand our knowledge on disease understanding, providing valuable insights into disease mechanisms and perhaps paving the way for novel therapeutic targets.

| S-EPMC10899781 | biostudies-literature

Genome-wide association studies of chronic kidney disease: what have we learned?

Project description:The past 3 years have witnessed a dramatic expansion in our knowledge of the genetic determinants of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). However, heritability estimates of eGFR indicate that we have only identified a small proportion of the total heritable contribution to the phenotypic variation. The majority of associations reported from genome-wide association studies identify genomic regions of interest and further work will be required to identify the causal variants responsible for a specific phenotype. Progress in this area is likely to stem from the identification of novel risk genotypes, which will offer insight into the pathogenesis of disease and potential novel therapeutic targets. Follow-up studies stimulated by findings from genome-wide association studies of kidney disease are already yielding promising results, such as the identification of an association between urinary uromodulin levels and incident CKD. Although this work is at an early stage, prospects for progress in our understanding of CKD and its treatment look more promising now than at any point in the past.

| S-EPMC4769862 | biostudies-literature

Molecular insights into genome-wide association studies of chronic kidney disease-defining traits.

Project description:Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.

| S-EPMC6250666 | biostudies-literature

Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease.

Project description:Chronic kidney disease (CKD) is a persistent impairment of kidney function. Genome-wide association studies (GWAS) have revealed multiple genetic loci associated with CKD susceptibility but the complete genetic basis is not yet clear. Since CKD shares risk factors with cardiovascular diseases and diabetes, there may be pleiotropic loci at play but may go undetected when using single phenotype GWAS. Here, we used multi-phenotype GWAS in the Norfolk Island isolate (n = 380) to identify new loci associated with CKD. We performed a principal components analysis on different combinations of 29 quantitative traits to extract principal components (PCs) representative of multiple correlated phenotypes. GWAS of a PC derived from glomerular filtration rate, serum creatinine, and serum urea identified a suggestive peak (pmin = 1.67 × 10-7) that mapped to KCNIP4. Inclusion of other secondary CKD measurements with these three kidney function traits identified the KCNIP4 locus with GWAS significance (pmin = 1.59 × 10-9). Finally, we identified a group of two SNPs with increased minor allele frequencies as potential functional variants. With the use of genetic isolate and the PCA-based multi-phenotype GWAS approach, we have revealed a potential pleotropic effect locus for CKD. Further studies are required to assess functional relevance of this locus.

| S-EPMC8484585 | biostudies-literature

Genome-wide association studies identify the role of caspase-9 in kidney disease.

Project description:Genome-wide association studies (GWAS) have identified hundreds of genetic risk regions for kidney dysfunction [estimated glomerular filtration rate (eGFR)]; however, the causal genes, cell types, and pathways are poorly understood. Integration of GWAS and human kidney expression of quantitative trait analysis using Bayesian colocations, transcriptome-wide association studies, and summary-based Mendelian randomization studies prioritized caspase-9 (CASP9) as a kidney disease risk gene. Human kidney single-cell epigenetic and immunostaining studies indicated kidney tubule cells as a disease-causing cell type. Mice with genetic deletion or pharmacological inhibition of CASP9 showed lower apoptosis while having improved mitophagy, resulting in dampened activation of cytosolic nucleotide sensing pathways (cGAS-STING), reduction of inflammation, and protection from acute kidney disease or renal fibrosis. In summary, here, we prioritized CASP9 as an eGFR GWAS target gene and demonstrated the causal role of CASP9 in kidney disease development via improving mitophagy and lowering inflammation and apoptosis.

| S-EPMC8570608 | biostudies-literature

An Overview of Genome-Wide Association Studies in Alzheimer's Disease.

Project description:Genome-wide association studies (GWASs) have revealed a plethora of putative susceptibility genes for Alzheimer's disease (AD). With the sole exception of the APOE gene, these AD susceptibility genes have not been unequivocally validated in independent studies. No single novel functional risk genetic variant has been identified. In this review, we evaluate recent GWASs of AD, and discuss their significance, limitations, and challenges in the investigation of the genetic spectrum of AD.

| S-EPMC5563735 | biostudies-other

Genome-wide association studies in Alzheimer's disease.

Project description:Genome-wide association studies (GWAS) have gained considerable momentum over the last couple of years for the identification of novel complex disease genes. In the field of Alzheimer's disease (AD), there are currently eight published and two provisionally reported GWAS, highlighting over two dozen novel potential susceptibility loci beyond the well-established APOE association. On the basis of the data available at the time of this writing, the most compelling novel GWAS signal has been observed in GAB2 (GRB2-associated binding protein 2), followed by less consistently replicated signals in galanin-like peptide (GALP), piggyBac transposable element derived 1 (PGBD1), tyrosine kinase, non-receptor 1 (TNK1). Furthermore, consistent replication has been recently announced for CLU (clusterin, also known as apolipoprotein J). Finally, there are at least three replicated loci in hitherto uncharacterized genomic intervals on chromosomes 14q32.13, 14q31.2 and 6q24.1 likely implicating the existence of novel AD genes in these regions. In this review, we will discuss the characteristics and potential relevance to pathogenesis of the outcomes of all currently available GWAS in AD. A particular emphasis will be laid on findings with independent data in favor of the original association.

| S-EPMC2758713 | biostudies-literature

Genome-wide epigenetic data facilitate understanding of disease susceptibility association studies.

Project description:Complex traits such as susceptibility to diseases are determined in part by variants at multiple genetic loci. Genome-wide association studies can identify these loci, but most phenotype-associated variants lie distal to protein-coding regions and are likely involved in regulating gene expression. Understanding how these genetic variants affect complex traits depends on the ability to predict and test the function of the genomic elements harboring them. Community efforts such as the ENCODE Project provide a wealth of data about epigenetic features associated with gene regulation. These data enable the prediction of testable functions for many phenotype-associated variants.

| S-EPMC3438926 | biostudies-other

Epigenome-wide association study of diabetic chronic kidney disease progression

Project description:Since the etiology of diabetic chronic kidney disease (CKD) is multifactorial, studies on DNA methylation for kidney function deterioration have rarely been performed despite the need for an epigenetic approach. Therefore, this study aimed to identify epigenetic markers associated with CKD progression based on the decline in the estimated glomerular filtration rate in diabetic CKD in Korea.

2023-05-10 | GSE230652 | GEO

Metabolite Genome-Wide Association Study for Indoleamine 2,3-Dioxygenase Activity Associated with Chronic Kidney Disease.

Project description:Chronic kidney disease (CKD) causes progressive damage to kidney function with increased inflammation. This process contributes to complex amino acid changes. Indoleamine 2,3-dioxygenase (IDO) has been proposed as a new biomarker of CKD in previous studies. In our research, we performed a metabolite genome-wide association study (mGWAS) to identify common and rare variants associated with IDO activity in a Korean population. In addition, single-nucleotide polymorphisms (SNPs) selected through mGWAS were further analyzed for associations with the estimated glomerular filtration rate (eGFR) and CKD. A total of seven rare variants achieved the genome-wide significance threshold (p < 1 × 10-8). Among them, four genes (TNFRSF19, LOC105377444, LOC101928535, and FSTL5) associated with IDO activity showed statistically significant associations with eGFR and CKD. Most of these rare variants appeared specifically in an Asian geographic region. Furthermore, 15 common variants associated with IDO activity were detected in this study and five novel genes (RSU1, PDGFD, SNX25, LOC107984031, and UBASH3B) associated with CKD and eGFR were identified. This study discovered several loci for IDO activity via mGWAS and provided insight into the underlying mechanisms of CKD through association analysis with CKD. To the best of our knowledge, this is the first study to suggest a genetic link between IDO activity and CKD through comparative and integrated analysis.

| S-EPMC8701662 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data