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 on HIV susceptibility, pathogenesis and pharmacogenomics.

ABSTRACT: Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication and pathogenesis. Recently, genome-wide association studies (GWAS) were utilized for unbiased searches at a genome-wide level to discover novel genetic factors and pathways involved in HIV-1 infection. This review gives an overview of findings from the GWAS performed on HIV infection, within different cohorts, with variable patient and phenotype selection. Furthermore, novel techniques and strategies in research that might contribute to the complete understanding of virus-host interactions and its role on the pathogenesis of HIV infection are discussed.

SUBMITTER: van Manen D

PROVIDER: S-EPMC3468375 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics.

van Manen Daniëlle D van 't Wout Angélique B AB Schuitemaker Hanneke H

Retrovirology 20120824

Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication and pathogenesis. Recently, genome-wide association studies (GWAS) were utilized for unbiased searches at a genome-wide level to discover novel genetic factors and pathways involved in HIV-1 infection ...[more]

PMID: 22920050

Similar Datasets

Pharmacogenomics discovery and implementation in genome-wide association studies era.

Project description:Clinical response to therapeutic treatments often varies among individual patients, ranging from beneficial effect to even fatal adverse reaction. Pharmacogenomics holds the promise of personalized medicine through elucidating genetic determinants responsible for pharmacological outcomes (e.g., cytotoxicities to anticancer drugs) and therefore guide the prescription decision prior to drug treatment. Besides traditional candidate gene-based approaches, technical advances have begun to allow application of whole-genome approaches to pharmacogenomic discovery. In particular, comprehensive understanding of human genetic variation provides the basis for applying GWAS (genome-wide association studies) in pharmacogenomic research to identify genomic loci associated with pharmacological phenotypes (e.g., individual dose requirement for warfarin). We therefore briefly reviewed the background for pharmacogenetic/pharmacogenomic research with statins and warfarin as examples for the GWAS discovery and their clinical implementation. In conclusion, with some challenges, whole-genome approaches such as GWAS have allowed unprecedented progress in identifying genetic variants associated with pharmacological phenotypes, as well as provided foundation for the next wave of pharmacogenomic discovery utilizing sequencing-based approaches. Furthermore, investigation of the complex interactions among genetic and epigenetic factors on the whole-genome scale will become the post-GWAS research focus for pharmacologic complex traits.

| S-EPMC3527666 | biostudies-literature

Pharmacogenomics of chronic hepatitis C therapy with genome-wide association studies.

Project description:Chronic hepatitis C (CHC) is a liver disease characterized by infection with the hepatitis C virus (HCV) persisting for more than six months. Patients with CHC often stop pursuing the pegylated interferon (peg-IFN) and ribavirin (RBV) treatment because of the high cost and associated adverse effects. Therefore, it is highly desirable, both clinically and economically, to establish the determinants of response to distinguish responders from nonresponders, and to predict the possible outcomes of the peg-IFN and RBV treatments. The aim of this study was to review recent data on the pharmacogenomics of the drug efficacy of IFN in CHC patients. Single nucleotide polymorphisms (SNPs) can be used to understand the relationship between genetic inheritance and IFN therapeutic response. In the recent advent of scientific research, the genome-wide association study (GWAS), which is an alternative to the candidate-gene approach, is widely utilized to examine hundreds of thousands of SNPs by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been employed to study the determinants of HCV's response to therapy. Several recent findings have demonstrated that some SNPs in the interleukin 28B gene are closely associated with IFN responsiveness. These results promise to lead to mechanistic findings related to IFN responsiveness in this disease, and will probably have major contributions for individualized medicine and therapeutic decision making.

| S-EPMC4863289 | biostudies-literature

A conceptual framework for pharmacodynamic genome-wide association studies in pharmacogenomics.

Project description:Genome-wide association studies (GWAS) have emerged as a powerful tool to identify loci that affect drug response or susceptibility to adverse drug reactions. However, current GWAS based on a simple analysis of associations between genotype and phenotype ignores the biochemical reactions of drug response, thus limiting the scope of inference about its genetic architecture. To facilitate the inference of GWAS in pharmacogenomics, we sought to undertake the mathematical integration of the pharmacodynamic (PD) process of drug reactions through computational models. By estimating and testing the genetic control of PD and pharmacokinetic (PK) parameters, this mechanistic approach does not only enhance the biological and clinical relevance of significant genetic associations, but also improve the statistical power and robustness of gene detection. This report discusses the general principle and development of PDs-based GWAS, highlights the practical use of this approach in addressing various pharmacogenomic problems, and suggests that this approach will be an important method to study the genetic architecture of drug responses or reactions.

| S-EPMC4029408 | 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

Genome-wide association studies identify new melanoma susceptibility loci

Project description: Not available

| S-EPMC3395392 | biostudies-literature

Genome-Wide Association and Transcriptome-Wide Association Studies Identify Novel Susceptibility Genes Contributing to Colorectal Cancer.

Project description:BackgroundColorectal cancer (CRC) is among the most common cancers diagnosed worldwide. Although genome-wide association studies have effectively identified the genetic basis of CRC, there is still unexplained variability in genetic risk. Transcriptome-wide association studies (TWAS) integrate summary statistics from CRC genome-wide association studies (GWAS) with gene expression data to prioritize these GWAS findings and uncover additional gene-trait correlations.MethodsFirst, we carried out a post-GWAS analysis using summary statistics from a large-scale GWAS of CRC (n = 4,562 cases, n = 382,756 controls). Second, combined with the expression weight sets from GTEx (v7), susceptibility genes were identified with the FUSION software. Colocalization, conditional and fine-mapping analyses, phenome-wide association study (pheWAS), and Mendelian randomization were employed to further characterize the observed correlations.ResultsIn the post-GWAS analyses, we first identified new genome-wide significant associations: three genomic risk loci were identified at 8q24.21 (rs6983267, P = 6.98 × 10-12), 15q13.3 (rs58658771, P = 1.40 × 10-10), and 18q21.1 (rs6507874, P = 1.91 × 10-14). In addition, the TWAS also identified four loci statistically significantly associated with CRC risk, largely explained by expression regulation, including six candidate genes (DUSP10, POU5F1B, C11orf53, COLCA1, COLCA2, and GREM1-AS1). We further discovered evidence that low expression of COLCA2 is correlated with CRC risk with Mendelian randomization.ConclusionsWe discovered novel CRC risk loci and candidate functional genes by merging gene expression and GWAS summary data, offering new insight into the molecular processes underlying CRC development. This makes it easier to prioritize potential genes for follow-up functional research in CRC.

| S-EPMC9270168 | biostudies-literature

Genome-wide association studies reveal susceptibility loci for digital dermatitis in Holstein cattle

Project description:Digital dermatitis (DD) causes lameness in dairy cattle. To detect quantitative trait loci (QTL) associated with DD, genome-wide association studies (GWAS) were performed using high density single nucleotide polymorphism (SNP) genotypes and binary case/control, quantitative (average number of FW per hoof trimming record), and recurrent (cases with  2 DD episodes vs. controls) phenotypes from cows across four dairies (controls n = 129 vs. FW n = 85). Linear mixed model (LMM) and random forest (RF) approaches identified top SNPs, which were used as predictors in Bayesian regression models to assess SNP predictive value. The LMM and RF analyses identified a QTL on BTA1 for the binary phenotype and on BTA2 for the quantitative phenotype. The binary and recurrent LMM GWASs also detected a QTL on BTA2 that was at a different position than the QTL from the quantitative phenotype analysis. The QTL on BTA1 lacked apparent candidate genes, whereas both QTL on BTA2 included genes associated with immune response and wound healing. Although larger sample sizes are necessary to reaffirm these small effect loci amidst a strong environmental effect, the sample cohort used in this study was sufficient for estimating SNP effects with high predictive value.

2020-12-07 | GSE159157 | GEO

Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes.

Project description:Adolescent idiopathic scoliosis (AIS) is an unexplained and common spinal deformity seen in otherwise healthy children. Its pathophysiology is poorly understood despite intensive investigation. Although genetic underpinnings are clear, replicated susceptibility loci that could provide insight into etiology have not been forthcoming. To address these issues, we performed genome-wide association studies (GWAS) of ?327 000 single nucleotide polymorphisms (SNPs) in 419 AIS families. We found strongest evidence of association with chromosome 3p26.3 SNPs in the proximity of the CHL1 gene (P < 8 × 10(-8) for rs1400180). We genotyped additional chromosome 3p26.3 SNPs and tested replication in two follow-up case-control cohorts, obtaining strongest results when all three cohorts were combined (rs10510181 odds ratio = 1.49, 95% confidence interval = 1.29-1.73, P = 2.58 × 10(-8)), but these were not confirmed in a separate GWAS. CHL1 is of interest, as it encodes an axon guidance protein related to Robo3. Mutations in the Robo3 protein cause horizontal gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Other top associations in our GWAS were with SNPs in the DSCAM gene encoding an axon guidance protein in the same structural class with Chl1 and Robo3. We additionally found AIS associations with loci in CNTNAP2, supporting a previous study linking this gene with AIS. Cntnap2 is also of functional interest, as it interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Our results suggest the relevance of axon guidance pathways in AIS susceptibility, although these findings require further study, particularly given the apparent genetic heterogeneity in this disease.

| S-EPMC3049353 | biostudies-literature

Automated quality control for genome wide association studies.

Project description:This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process.

| S-EPMC5007749 | biostudies-other

Genome-Wide Association Studies Reveal Susceptibility Loci for Digital Dermatitis in Holstein Cattle.

Project description:Digital dermatitis (DD) causes lameness in dairy cattle. To detect the quantitative trait loci (QTL) associated with DD, genome-wide association studies (GWAS) were performed using high-density single nucleotide polymorphism (SNP) genotypes and binary case/control, quantitative (average number of FW per hoof trimming record) and recurrent (cases with ≥2 DD episodes vs. controls) phenotypes from cows across four dairies (controls n = 129 vs. FW n = 85). Linear mixed model (LMM) and random forest (RF) approaches identified the top SNPs, which were used as predictors in Bayesian regression models to assess the SNP predictive value. The LMM and RF analyses identified QTL regions containing candidate genes on Bos taurus autosome (BTA) 2 for the binary and recurrent phenotypes and BTA7 and 20 for the quantitative phenotype that related to epidermal integrity, immune function, and wound healing. Although larger sample sizes are necessary to reaffirm these small effect loci amidst a strong environmental effect, the sample cohort used in this study was sufficient for estimating SNP effects with a high predictive value.

| S-EPMC7693332 | 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