Journal ArticleDOI
Recent innovations and in-depth aspects of post-genome wide association study (Post-GWAS) to understand the genetic basis of complex phenotypes.
TLDR
In this paper, the authors highlight how post-GWAS analysis can be used to make sense of the obtained associations and discuss the challenges of identifying interactions between genetic mutations (epistasis) and mutations of loci affecting more than one trait (pleiotropy) as underlying causes of cross-phenotype associations.Abstract:
In the past decade, the high throughput and low cost of sequencing/genotyping approaches have led to the accumulation of a large amount of data from genome-wide association studies (GWASs). The first aim of this review is to highlight how post-GWAS analysis can be used make sense of the obtained associations. Novel directions for integrating GWAS results with other resources, such as somatic mutation, metabolite-transcript, and transcriptomic data, are also discussed; these approaches can help us move beyond each individual data point and provide valuable information about complex trait genetics. In addition, cross-phenotype association tests, when the loci detected by GWASs have significant associations with multiple traits, are reviewed to provide biologically informative results for use in real-time applications. This review also discusses the challenges of identifying interactions between genetic mutations (epistasis) and mutations of loci affecting more than one trait (pleiotropy) as underlying causes of cross-phenotype associations; these challenges can be overcome using post-GWAS analysis. Genetic similarities between phenotypes that can be revealed using post-GWAS analysis are also discussed. In summary, different methodologies of post-GWAS analysis are now available, enhancing the value of information obtained from GWAS results, and facilitating application in both humans and nonhuman species. However, precise methods still need to be developed to overcome challenges in the field and uncover the genetic underpinnings of complex traits.read more
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Journal ArticleDOI
Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk
Xianyong Yin,Debraj Bose,Annie Kwon,Sarah C. Hanks,Anne U. Jackson,Heather M. Stringham,Ryan P. Welch,Anniina Oravilahti,Lilian Fernandes Silva,Adam E. Locke,Christian Fuchsberger,S. Service,Michael R. Erdos,Lori L. Bonnycastle,Johanna Kuusisto,Nathan O. Stitziel,Ira M. Hall,Jean Morrison,Samuli Ripatti,Aarno Palotie,Nelson B. Freimer,Francis S. Collins,Karen L. Mohlke,Laura J. Scott,Eric B. Fauman,Charles F. Burant,Michael Boehnke,Markku Laakso,Xiaoquan Wen +28 more
TL;DR: In this article , the authors performed probabilistic transcriptome-wide association and locus-level colocalization analyses to integrate transcriptomics results for 49 tissues in 706 individuals from the GTEx project, metabolomics results from 1,391 plasma metabolites in 6,136 Finnish men from the METSIM study, and GWAS results for 2,861 disease traits in 260,405 Finnish individuals from FinnGen study.
Journal ArticleDOI
A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci
Elisabeth J. van Bree,Rita Leonor Franco Paulo Guimarães,Mischa Lundberg,Elena R Blujdea,Jimi L. Rosenkrantz,F. G. White,Josse Poppinga,Paula Ferrer-Raventós,Anne-Fleur E Schneider,Isabella Clayton,David Haussler,Marcel J. T. Reinders,Henne Holstege,Adam D. Ewing,Colette Moses,Frank M. J. Jacobs +15 more
TL;DR: A novel layer of genetic variation in transposable elements is revealed that may contribute to identification of the structural variants that are the actual drivers of disease associations of GWAS loci.
Journal ArticleDOI
Trade-offs in the genetic control of functional and nutritional quality traits in UK winter wheat
TL;DR: In this paper , the authors investigated the correlated relationships among several milling and baking traits as well as mineral density in refined white and whole grain flour, and determined their pleiotropic genetic control in a multi-parent population over two trial years with direct application to practical breeding.
Journal ArticleDOI
Dissecting Meta-Analysis in GWAS Era: Bayesian Framework for Gene/Subnetwork-Specific Meta-Analysis
Emile R. Chimusa,Joel Defo +1 more
TL;DR: AncMETA, a Bayesian graph-based framework, is proposed to perform the gene/pathway-specific meta-analysis by combining the effect size of multiple SNPs within genes, and genes within subnetwork/pathways across multiple independent population GWASs to deconvolute the interactions between genes underlying the pathogenesis of complex diseases across human populations.
Journal ArticleDOI
Integrating plant and fungal quantitative genetics to improve the ecological and agricultural applications of mycorrhizal symbioses.
Erica McGale,Ian R. Sanders +1 more
TL;DR: In this article , the availability of Rhizophagus irregularis mycorrhizal isolates, with genomic information, makes dual-genome methods with beneficial mutualists accessible and imminent.
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TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.