An R Package for Analysis of Whole-Genome Association Studies
Human HeredityPublished 1 January 2007
David Clayton, H.T. Leung
Citations99
SJR quartileQ3
SJR score0.48
SNIP0.44
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Data classes in which each genotype call is stored as a single byte are implemented to facilitate the analysis of whole genome association studies in the R language for statistical computing.
Abstract
OBJECTIVE: To provide data classes and methods to facilitate the analysis of whole genome association studies in the R language for statistical computing. METHODS: We have implemented data classes in which each genotype call is stored as a single byte. At this density, data for single chromosomes derived from large studies and new high-throughput gene chip platforms can be handled in memory. We use the object-oriented programming model introduced with version 4 of the S-plus package, usually termed 'S4 methods'. RESULTS: At the current state of development the package only supports population-based studies, although we would hope to provide support for family-based studies soon. Both quantitative and qualitative phenotypes may be analysed. Flexible association testing functions are provided which can carry out single SNP tests which control for potential confounding by quantitative and qualitative covariates. Tests involving several SNPs taken together as 'tags' are also supported. Efficient calculation of pair-wise linkage disequilibrium measures is implemented and data input functions include a function which can download data directly from the international HapMap project website.
Keywords
Biochemistry, Genetics and Molecular Biology
BioinformaticsHaploview: analysis and visualization of LD and haplotype maps
14,738 Citations2004Jeffrey C. Barrett, Ben Fry +2 more
Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.
Nature GeneticsPrincipal components analysis corrects for stratification in genome-wide association studies
10,720 Citations2006Alkes L. Price, Nick J. Patterson +4 more
This work describes a method that enables explicit detection and correction of population stratification on a genome-wide scale and uses principal components analysis to explicitly model ancestry differences between cases and controls.
NatureThe International HapMap Project
6,170 Citations2003Richard A. Gibbs, John W. Belmont +181 more
The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Journal of the American Statistical AssociationChi-Square Tests with One Degree of Freedom; Extensions of the Mantel-Haenszel Procedure
2,627 Citations1963Nathan Mantel
Extensions of application include comparisons of age-adjusted death rates, life-table analyses, comparisons of two sets of quantal dosage-response data, and miscellaneous laboratory applications as appropriate.
Springer series in statisticsThe Generalization of Student’s Ratio
1,103 Citations1992Harold Hotelling
BiometrikaLogistic disease incidence models and case-control studies
1,088 Citations1979Ross L. Prentice, Ronald Pyke
It is shown that the odds ratio estimators and their asymptotic variance matrices may be obtained by applying the original logistic regression model to the case-control study as if the data had been obtained in a prospective study.
GenomicsA Comparison of Linkage Disequilibrium Measures for Fine-Scale Mapping
1,052 Citations1995Bernie Devlin, Neil Risch
This work investigates the simple mapping properties of five disequ equilibrium measures, the correlation coefficient delta, Lewontin's D', the robust formulation of the population attributable risk delta, Yule's Q, and Kaplan and Weir's proportional difference d under the assumption of initial complete disequilibrium between disease and marker loci, and indicates that delta is a superior measure for fine mapping.
HeredityTesting for linkage disequilibrium in genotypic data using the Expectation-Maximization algorithm
575 Citations1996Montgomery Slatkin, Laurent Excoffier
It is concluded that with highly polymorphic loci, the EM algorithm does lead to a useful test for linkage disequilibrium, but that it is necessary to find the empirical distribution of likelihood ratios in order to perform a test of significance correctly.
Nature GeneticsPopulation structure, differential bias and genomic control in a large-scale, case-control association study
532 Citations2005David Clayton, Neil Walker +17 more
To avoid excluding SNPs and losing valuable information, the genomic control method is extended by applying a variable downweighting to each SNP, which explains part of the significant +11.2% inflation of test statistics the authors observed in an analysis of 6,322 nonsynonymous SNPs.
Human HeredityDetecting Disease Associations due to Linkage Disequilibrium Using Haplotype Tags: A Class of Tests and the Determinants of Statistical Power
422 Citations2003Juliet Chapman, Jason D. Cooper +2 more
The role of the R2 measure of association between a causal locus and various methods of scoring of marker haplotypes is highlighted and the simplest method of scoring (locus coding), which does not require phase resolution, is shown generally to be more powerful than scoring methods that include haplotype information.
Genetic EpidemiologyUse of unphased multilocus genotype data in indirect association studies
187 Citations2004David Clayton, Juliet Chapman +1 more
This work reviews recent work on the value of the marker haplotype information, and relates these analyses to alternative approaches to haplotype analysis, namely those based on haplotype similarity and those inspired by cladistics.
Topics in Modelling of Clustered Data
148 Citations2002Marc Aerts, Helena Geys +2 more
The American Journal of Human GeneticsGeneralized T2 Test for Genome Association Studies
124 Citations2002Momiao Xiong, Jinying Zhao +1 more
A generalized T2 statistic is presented, which can utilize multiple SNP markers simultaneously and considers the effects of multiple disease-susceptibility loci and has a close relationship to discriminant analysis and common measure of genetic distance.
The American Journal of Human GeneticsGenome Association Studies of Complex Diseases by Case-Control Designs
81 Citations2003Ruzong Fan, Michael Knapp
High-resolution LD-mapping methods, for complex diseases, based on haplotype maps or microsatellite marker maps, are investigated, to explore test statistics that combine information from haplotype blocks or multiple markers.
The American Journal of Human GeneticsImproved Power Offered by a Score Test for Linkage Disequilibrium Mapping of Quantitative-Trait Loci by Selective Genotyping
45 Citations2006Chris Wallace, Juliet Chapman +1 more
Hotelling's T(2) test, recently proposed for association studies of one or several tagging single-nucleotide polymorphisms in a prospective (i.e., trait given genotype) design, can also be applied to the retrospective retrospective selective-genotyping design, and simulation is used to demonstrate its improved power over existing methods.
The American Journal of Human GeneticsLinkage Analysis Using Co-Phenotypes in the BRIGHT Study Reveals Novel Potential Susceptibility Loci for Hypertension
24 Citations2006Chris Wallace, Mingzhan Xue +17 more
This is the first identity-by-descent regression analysis of hypertension to the authors' knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits.