Journal ArticleDOI
Detecting epistasis in human complex traits
TLDR
The purpose of this Review is to summarize recent directions in methodology for detecting epistasis and to discuss evidence of the role of epistasis in human complex trait variation.Abstract:
Genome-wide association studies (GWASs) have become the focus of the statistical analysis of complex traits in humans, successfully shedding light on several aspects of genetic architecture and biological aetiology. Single-nucleotide polymorphisms (SNPs) are usually modelled as having additive, cumulative and independent effects on the phenotype. Although evidently a useful approach, it is often argued that this is not a realistic biological model and that epistasis (that is, the statistical interaction between SNPs) should be included. The purpose of this Review is to summarize recent directions in methodology for detecting epistasis and to discuss evidence of the role of epistasis in human complex trait variation. We also discuss the relevance of epistasis in the context of GWASs and potential hazards in the interpretation of statistical interaction terms.read more
Citations
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Journal ArticleDOI
Benefits and limitations of genome-wide association studies.
Vivian W.Y. Tam,Nikunj Patel,Michelle Turcotte,Yohan Bossé,Guillaume Paré,David Meyre,David Meyre +6 more
TL;DR: This Review comprehensively assess the benefits and limitations of GWAS in human populations and discusses the relevance of performing more GWAS, with a focus on the cardiometabolic field.
Journal ArticleDOI
A population genetic interpretation of GWAS findings for human quantitative traits.
TL;DR: This work solves the model for the phenotypic distribution and allelic dynamics at steady state and derive robust, closed-form solutions for summary statistics of the genetic architecture of a focal trait that arises under stabilizing selection in a multidimensional trait space.
Journal ArticleDOI
Targeted capture in evolutionary and ecological genomics
Matthew R. Jones,Jeffrey M. Good +1 more
TL;DR: This work aims to increase the accessibility of targeted capture to researchers working in nonmodel taxa by discussing capture methods that circumvent the need of a reference genome, and highlight the evolutionary and ecological applications where this approach is emerging as a powerful sequencing strategy.
Journal ArticleDOI
Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases.
Oscar Franzén,Raili Ermel,Raili Ermel,Ariella Cohain,Nicholas K. Akers,Antonio Fabio Di Narzo,Husain A. Talukdar,Hassan Foroughi-Asl,Claudia Giambartolomei,John F. Fullard,Katyayani Sukhavasi,Sulev Kõks,Li-Ming Gan,Chiara Giannarelli,Jason C. Kovacic,Christer Betsholtz,Bojan Losic,Tom Michoel,Ke Hao,Panos Roussos,Panos Roussos,Josefin Skogsberg,Arno Ruusalepp,Arno Ruusalepp,Eric E. Schadt,Johan Björkegren +25 more
TL;DR: Gene expression traits associated with CMD risk single-nucleotide polymorphism (SNPs) identified by GWAS were more extensively found in STARNET than in tissue- and disease-unspecific gene-tissue expression studies, indicating sharing of downstream cis-/trans-gene regulation across tissues and CMDs.
Journal ArticleDOI
Network approaches to systems biology analysis of complex disease: integrative methods for multi-omics data.
TL;DR: In this article, the authors review extant and emerging network approaches that can be applied across multiple biological layers to facilitate a more comprehensive and integrative multilayered omics analysis of complex diseases.
References
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Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
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.
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Introduction to quantitative genetics
TL;DR: The genetic constitution of a population: Hardy-Weinberg equilibrium and changes in gene frequency: migration mutation, changes of variance, and heritability are studied.
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Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
Shaun Purcell,Shaun Purcell,Naomi R. Wray,Jennifer Stone,Jennifer Stone,Peter M. Visscher,Michael Conlon O'Donovan,Patrick F. Sullivan,Pamela Sklar,Pamela Sklar,Douglas M. Ruderfer,Andrew McQuillin,Derek W. Morris,Colm O'Dushlaine,Aiden Corvin,Peter Holmans,Stuart MacGregor,Hugh Gurling,Douglas Blackwood,Nicholas John Craddock,Michael Gill,Christina M. Hultman,Christina M. Hultman,George Kirov,Paul Lichtenstein,Walter J. Muir,Michael John Owen,Carlos N. Pato,Edward M. Scolnick,Edward M. Scolnick,David St Clair,Nigel Williams,Lyudmila Georgieva,Ivan Nikolov,Nadine Norton,Hywel Williams,Draga Toncheva,Vihra Milanova,Emma Flordal Thelander,Patrick Sullivan,Elaine Kenny,Emma M. Quinn,Khalid Choudhury,Susmita Datta,Jonathan Pimm,Srinivasa Thirumalai,Vinay Puri,Robert Krasucki,Jacob Lawrence,Digby Quested,Nicholas Bass,Caroline Crombie,Gillian Fraser,Soh Leh Kuan,Nicholas Walker,Kevin A. McGhee,Ben S. Pickard,P. Malloy,Alan W Maclean,Margaret Van Beck,Michele T. Pato,Helena Medeiros,Frank A. Middleton,Célia Barreto Carvalho,Christopher P. Morley,Ayman H. Fanous,David V. Conti,James A. Knowles,Carlos Ferreira,António Macedo,M. Helena Azevedo,Andrew Kirby,Andrew Kirby,Manuel A. R. Ferreira,Manuel A. R. Ferreira,Mark J. Daly,Mark J. Daly,Kimberly Chambert,Finny G Kuruvilla,Stacey Gabriel,Kristin G. Ardlie,Jennifer L. Moran +81 more
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Journal ArticleDOI
Five years of GWAS discovery
Peter M. Visscher,Peter M. Visscher,Matthew A. Brown,Mark I. McCarthy,Mark I. McCarthy,Jian Yang +5 more
TL;DR: The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs), which were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders.
Journal ArticleDOI
Heritability in the genomics era — concepts and misconceptions
TL;DR: This work has shown that despite continuous misunderstandings and controversies over its use and application, heritability remains key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine.
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