Genome-Wide Association Studies in Disease Risk Calculation: The Role of Bioinformatics in Patient Care

2011 ◽  
pp. 103-129
Author(s):  
Todd L. Edwards ◽  
Digna R. Velez Edwards ◽  
Marylyn DeRiggi Ritchie
Keyword(s):  
Patient Care ◽  
Disease Risk ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Risk Calculation ◽  
Genome Wide

scholarly journals Current knowledge in hypertension genetics: mosaic theory, candidate genes and genome-wide association studies

2020 ◽  
Vol 26 (5) ◽  
pp. 490-500
Author(s):  
A. O. Konradi
Keyword(s):  
Candidate Genes ◽  
High Performance ◽  
New Technologies ◽  
Current Knowledge ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Modern Approach ◽  
Genome Wide

The article reviews monogenic forms of hypertension, data on the role of heredity of essential hypertension and candidate genes, as well as genome-wide association studies. Modern approach for the role of genetics is driven by implementation of new technologies and their productivity. High performance speed of new technologies like genome-wide association studies provide data for better knowledge of genetic markers of hypertension. The major goal nowadays for research is to reveal molecular pathways of blood pressure regulation, which can help to move from populational to individual level of understanding of pathogenesis and treatment targets.

Role of Bioinformatics in Genome-wide Association Studies

2011 ◽  
Author(s):  
Diane Gilbert-Diamond ◽  
Folkert W Asselbergs ◽  
Scott M Williams ◽  
Jason H Moore
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Sex Differences in Urate Handling

2020 ◽  
Vol 21 (12) ◽  
pp. 4269 ◽  
Author(s):  
Victoria L. Halperin Kuhns ◽  
Owen M. Woodward
Keyword(s):  
Sex Differences ◽  
Disease Risk ◽  
Association Studies ◽  
Elevated Serum ◽  
Serum Urate ◽  
Genome Wide Association Studies ◽  
Renal Handling ◽  
Physiological Regulation ◽  
Genome Wide

Hyperuricemia, or elevated serum urate, causes urate kidney stones and gout and also increases the incidence of many other conditions including renal disease, cardiovascular disease, and metabolic syndrome. As we gain mechanistic insight into how urate contributes to human disease, a clear sex difference has emerged in the physiological regulation of urate homeostasis. This review summarizes our current understanding of urate as a disease risk factor and how being of the female sex appears protective. Further, we review the mechanisms of renal handling of urate and the significant contributions from powerful genome-wide association studies of serum urate. We also explore the role of sex in the regulation of specific renal urate transporters and the power of new animal models of hyperuricemia to inform on the role of sex and hyperuricemia in disease pathogenesis. Finally, we advocate the use of sex differences in urate handling as a potent tool in gaining a further understanding of physiological regulation of urate homeostasis and for presenting new avenues for treating the constellation of urate related pathologies.

scholarly journals Challenges and progress in interpretation of non-coding genetic variants associated with human disease

2017 ◽  
Vol 242 (13) ◽  
pp. 1325-1334 ◽  
Author(s):  
Yizhou Zhu ◽  
Cagdas Tazearslan ◽  
Yousin Suh
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Disease Risk ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Functional Interpretation ◽  
Genome Wide ◽  
Coding Variants

Genome-wide association studies have shown that the far majority of disease-associated variants reside in the non-coding regions of the genome, suggesting that gene regulatory changes contribute to disease risk. To identify truly causal non-coding variants and their affected target genes remains challenging but is a critical step to translate the genetic associations to molecular mechanisms and ultimately clinical applications. Here we review genomic/epigenomic resources and in silico tools that can be used to identify causal non-coding variants and experimental strategies to validate their functionalities. Impact statement Most signals from genome-wide association studies (GWASs) map to the non-coding genome, and functional interpretation of these associations remained challenging. We reviewed recent progress in methodologies of studying the non-coding genome and argued that no single approach allows one to effectively identify the causal regulatory variants from GWAS results. By illustrating the advantages and limitations of each method, our review potentially provided a guideline for taking a combinatorial approach to accurately predict, prioritize, and eventually experimentally validate the causal variants.

scholarly journals Adaptive growth homeostasis in response to drought in Iberian Arabidopsis accessions

2021 ◽  
Author(s):  
Ángel Ferrero-Serrano ◽  
Sarah M Assmann
Keyword(s):  
Leaf Area ◽  
Stress Responses ◽  
Association Studies ◽  
Transport Processes ◽  
Functional Enrichment ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Intrinsic Water Use Efficiency

Plants respond to environmental fluctuations through plastic phenotypic shifts. Whether a plastic response upon environmental variability is adaptive or not has been subject to debate. Using a set of Iberian Arabidopsis accessions, we quantified an interplay between passive plastic reductions in leaf areas that we found typical of accessions from productive environments and homeostatic leaf areas responses to drought typified by accessions originating from unproductive environments. Results from Genome-Wide Association Studies (GWAS) and Transcriptome Wide Association Studies (TWAS) highlight the role of auxin-related processes and, in particular, the possible role of the SMALL AUXIN UP RNA 26 (SAUR26) gene in the regulation of the observed plastic responses. Homeostatic responses in leaf area potential following drought were typical of accessions with lower leaf area potential under well-watered conditions. Transcripts that were negatively associated with leaf area potential and positively associated with homeostatic and positive leaf area plasticity following drought showed functional enrichment in ion transport processes. We hypothesized that the contrasting plastic and homeostatic responses in leaf area potential were associated with differential intrinsic water use efficiency (WUEi). We confirmed this relationship in a metanalysis conducted using previously published δ13C measurements. Our results highlight the adaptive role of homeostatic leaf area response to water depletion arising from increased WUEi. The concerted utilization of Genome-Wide Association Studies (GWAS), Transcriptome Wide Association Studies (TWAS), and expression Genome-Wide Association Studies (eGWAS) allows integration of phenotype, genotype, and transcript abundance to identify both "plasticity genes" and "homeostasis genes" associated with drought stress responses.

scholarly journals Discovering patterns of pleiotropy in genome-wide association studies

2018 ◽  
Author(s):  
Jianan Zhana ◽  
Jessica van Setten ◽  
Jennifer Brody ◽  
Brenton Swenson ◽  
Anne M. Butler ◽  
...  
Keyword(s):  
Gold Standard ◽  
Disease Risk ◽  
Association Studies ◽  
Meta Analysis ◽  
Linkage Disequilibrium Block ◽  
Genome Wide Association ◽  
Superior Performance ◽  
Great Success ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractMotivationGenome-wide association studies have had great success in identifying human genetic variants associated with disease, disease risk factors, and other biomedical phenotypes. Many variants are associated with multiple traits, even after correction for trait-trait correlation. Discovering subsets of variants associated with a shared subset of phenotypes could help reveal disease mechanisms, suggest new therapeutic options, and increase the power to detect additional variants with similar pattern of associations. Here we introduce two methods based on a Bayesian framework, SNP And Pleiotropic PHenotype Organization (SAPPHO), one modeling independent phenotypes (SAPPHO-I) and the other incorporating a full phenotype covariance structure (SAPPHO-C). These two methods learn patterns of pleiotropy from genotype and phenotype data, using identified associations to discover additional associations with shared patterns.ResultsThe SAPPHO methods, along with other recent approaches for pleiotropic association tests, were assessed using data from the Atherosclerotic Risk in Communities (ARIC) study of 8,000 individuals, whose gold-standard associations were provided by meta-analysis of 40,000 to 100,000 individuals from the CHARGE consortium. Using power to detect gold-standard associations at genome-wide significance (0.05 family-wise error rate) as a metric, SAPPHO performed best. The SAPPHO methods were also uniquely able to select the most significant variants in a parsimonious model, excluding other less likely variants within a linkage disequilibrium block. For meta-analysis, the SAPPHO methods implement summary modes that use sufficient statistics rather than full phenotype and genotype data. Meta-analysis applied to CHARGE detected 16 additional associations to the gold-standard loci, as well as 124 novel loci, at 0.05 false discovery rate. Reasons for the superior performance were explored by performing simulations over a range of scenarios describing different genetic architectures. With SAPPHO we were able to learn genetic structures that were hidden using the traditional univariate tests.Availabilityhttps://bitbucket.org/baderlab/fast/wiki/Home. SAPPHO software is available under the GNU General Public License, v2.

Primary Sjögren Syndrome: Etiology and Pathogenesis

2017 ◽  
Author(s):  
E. William St. Clair ◽  
Stephanie L Giattino
Keyword(s):  
Animal Models ◽  
Disease Risk ◽  
Association Studies ◽  
Sjögren Syndrome ◽  
Genome Wide Association ◽  
Inflammatory Disorder ◽  
Sjogren Syndrome ◽  
Genome Wide Association Studies ◽  
Primary Sjögren Syndrome ◽  
Genome Wide

Primary Sjögren syndrome is a chronic inflammatory disorder of the lacrimal and salivary glands resulting in oral and ocular dryness. It also has extraglandular manifestations that may affect the lung, kidneys, nervous system, and other organs. The etiology and pathogenesis of primary Sjögren syndrome are incompletely understood. A working hypothesis considers the disease to be driven by a complex interplay of environmental, genetic, and epigenetic factors. Recent genome-wide association studies confirm the previously shown contribution of major histocompatibility (MHC) locus to disease susceptibility and illuminate several non-MHC loci, which add to disease risk. New gene expression studies of peripheral blood and salivary gland tissue provide further molecular detail about the role of innate and adaptive immune pathways involved in disease mechanisms. In particular, upregulated expression of interferon and B cell–activating factor appear to play key roles in this process. Despite their drawbacks, experimental animal models continue to stimulate new lines of research that are advancing our understanding of human disease. This knowledge has been translated into new therapeutic approaches currently under evaluation in clinical trials. This review contains 5 figures, 2 tables, and 67 references. Key words: adaptive immunity, animal models, epigenetics, genome-wide association studies, innate immunity, interferon signature, lymphoma pathogenesis, nucleic acid sensing, primary Sjögren syndrome 

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