Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GLOGS: a fast and powerful method for GWAS of binary traits with risk covariates in related populations.

ABSTRACT: Mixed model-based approaches to genome-wide association studies (GWAS) of binary traits in related individuals can account for non-genetic risk factors in an integrated manner. However, they are technically challenging. GLOGS (Genome-wide LOGistic mixed model/Score test) addresses such challenges with efficient statistical procedures and a parallel implementation. GLOGS has high power relative to alternative approaches as risk covariate effects increase, and can complete a GWAS in minutes.Source code and documentation are provided at http://www.bioinformatics.org/~stanhope/GLOGS.

SUBMITTER: Stanhope SA

PROVIDER: S-EPMC3356846 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

GLOGS: a fast and powerful method for GWAS of binary traits with risk covariates in related populations.

Stanhope Stephen A SA Abney Mark M

Bioinformatics (Oxford, England) 20120419 11

<h4>Summary</h4>Mixed model-based approaches to genome-wide association studies (GWAS) of binary traits in related individuals can account for non-genetic risk factors in an integrated manner. However, they are technically challenging. GLOGS (Genome-wide LOGistic mixed model/Score test) addresses such challenges with efficient statistical procedures and a parallel implementation. GLOGS has high power relative to alternative approaches as risk covariate effects increase, and can complete a GWAS i ...[more]

PMID: 22522135

Similar Datasets

On powerful GWAS in admixed populations.

Project description: Not available

| S-EPMC8939372 | biostudies-literature

A fast linkage method for population GWAS cohorts with related individuals.

Project description:Linkage analysis, a class of methods for detecting co-segregation of genomic segments and traits in families, was used to map disease-causing genes for decades before genotyping arrays and dense SNP genotyping enabled genome-wide association studies in population samples. Population samples often contain related individuals, but the segregation of alleles within families is rarely used because traditional linkage methods are computationally inefficient for larger datasets. Here, we describe Population Linkage, a novel application of Haseman-Elston regression as a method of moments estimator of variance components and their standard errors. We achieve additional computational efficiency by using modern methods for detection of IBD segments and variance component estimation, efficient preprocessing of input data, and minimizing redundant numerical calculations. We also refined variance component models to account for the biases in population-scale methods for IBD segment detection. We ran Population Linkage on four blood lipid traits in over 70,000 individuals from the HUNT and SardiNIA studies, successfully detecting 25 known genetic signals. One notable linkage signal that appeared in both was for low-density lipoprotein (LDL) cholesterol levels in the region near the gene APOE (LOD = 29.3, variance explained = 4.1%). This is the region where the missense variants rs7412 and rs429358, which together make up the ε2, ε3, and ε4 alleles each account for 2.4% and 0.8% of variation in circulating LDL cholesterol. Our results show the potential for linkage analysis and other large-scale applications of method of moments variance components estimation.

| S-EPMC10027464 | biostudies-literature

A fast, powerful method for detecting identity by descent.

Project description:We present a method, fastIBD, for finding tracts of identity by descent (IBD) between pairs of individuals. FastIBD can be applied to thousands of samples across genome-wide SNP data and is significantly more powerful for finding short tracts of IBD than existing methods for finding IBD tracts in such data. We show that fastIBD can detect facets of population structure that are not revealed by other methods. In the Wellcome Trust Case Control Consortium bipolar disorder case-control data, we find a genome-wide excess of IBD in case-case pairs of individuals compared to control-control pairs. We show that this excess can be explained by the geographical clustering of cases. We also show that it is possible to use fastIBD to generate highly accurate estimates of genome-wide IBD sharing between pairs of distant relatives. This is useful for estimation of relationship and for adjusting for relatedness in association studies. FastIBD is incorporated in the freely available Beagle software package.

| S-EPMC3035716 | biostudies-literature

A Powerful Method To Test Associations Between Ordinal Traits and Genotypes.

Project description:The methods commonly used to test the associations between ordinal phenotypes and genotypes often treat either the ordinal phenotype or the genotype as continuous variables. To address limitations of these approaches, we propose a model where both the ordinal phenotype and the genotype are viewed as manifestations of an underlying multivariate normal random variable. The proposed method allows modeling the ordinal phenotype, the genotype and covariates jointly. We employ the generalized estimating equation technique and M-estimation theory to estimate the model parameters and deduce the corresponding asymptotic distribution. Numerical simulations and real data applications are also conducted to compare the performance of the proposed method with those of methods based on the logit and probit models. Even though there may be potential limitations in Type I error rate control for our method, the gains in power can prove its practical value in case of exactly ordinal phenotypes.

| S-EPMC6686925 | biostudies-literature

A Fast and Powerful Empirical Bayes Method for Genome-Wide Association Studies.

Project description:Linear mixed model (LMM) is an efficient method for GWAS. There are numerous forms of LMM-based GWAS methods. However, improving statistical power and computing efficiency have always been the research hotspots of the LMM-based GWAS methods. Here, we proposed a fast empirical Bayes method, which is based on linear mixed models. We call it Fast-EB-LMM in short. The novelty of this method is that it uses a modified kinship matrix accounting for individual relatedness to avoid competition between the locus of interest and its counterpart in the polygene. This property has increased statistical power. We adopted two special algorithms to ease the computational burden: Eigenvalue decomposition and Woodbury matrix identity. Simulation studies showed that Fast-EB-LMM has significantly increased statistical power of marker detection and improved computational efficiency compared with two widely used GWAS methods, EMMA and EB. Real data analyses for two carcass traits in a Chinese Simmental beef cattle population showed that the significant single-nucleotide polymorphisms (SNPs) and candidate genes identified by Fast-EB-LMM are highly consistent with results of previous studies. We therefore believe that the Fast-EB-LMM method is a reliable and efficient method for GWAS.

| S-EPMC6616871 | biostudies-literature

A Fast EM Algorithm for Fitting Joint Models of a Binary Response and Multiple Longitudinal Covariates Subject to Detection Limits.

Project description:Joint modeling techniques have become a popular strategy for studying the association between a response and one or more longitudinal covariates. Motivated by the GenIMS study, where it is of interest to model the event of survival using censored longitudinal biomarkers, a joint model is proposed for describing the relationship between a binary outcome and multiple longitudinal covariates subject to detection limits. A fast, approximate EM algorithm is developed that reduces the dimension of integration in the E-step of the algorithm to one, regardless of the number of random effects in the joint model. Numerical studies demonstrate that the proposed approximate EM algorithm leads to satisfactory parameter and variance estimates in situations with and without censoring on the longitudinal covariates. The approximate EM algorithm is applied to analyze the GenIMS data set.

| S-EPMC4295570 | biostudies-literature

QT-GWAS: A novel method for unveiling biosynthetic loci affecting qualitative metabolic traits.

Project description:Although the plant kingdom provides an enormous diversity of metabolites with potentially beneficial applications for humankind, a large fraction of these metabolites and their biosynthetic pathways remain unknown. Resolving metabolite structures and their biosynthetic pathways is key to gaining biological understanding and to allow metabolic engineering. In order to retrieve novel biosynthetic genes involved in specialized metabolism, we developed a novel untargeted method designated as qualitative trait GWAS (QT-GWAS) that subjects qualitative metabolic traits to a genome-wide association study, while the conventional metabolite GWAS (mGWAS) mainly considers the quantitative variation of metabolites. As a proof of the validity of QT-GWAS, 23 and 15 of the retrieved associations identified in Arabidopsis thaliana by QT-GWAS and mGWAS, respectively, were supported by previous research. Furthermore, seven gene-metabolite associations retrieved by QT-GWAS were confirmed in this study through reverse genetics combined with metabolomics and/or in vitro enzyme assays. As such, we established that CYTOCHROME P450 706A5 (CYP706A5) is involved in the biosynthesis of chroman derivatives, UDP-GLYCOSYLTRANSFERASE 76C3 (UGT76C3) is able to hexosylate guanine in vitro and in planta, and SULFOTRANSFERASE 202B1 (SULT202B1) catalyzes the sulfation of neolignans in vitro. Collectively, our study demonstrates that the untargeted QT-GWAS method can retrieve valid gene-metabolite associations at the level of enzyme-encoding genes, even new associations that cannot be found by the conventional mGWAS, providing a new approach for dissecting qualitative metabolic traits.

| S-EPMC7614782 | biostudies-literature

Marginal methods for clustered longitudinal binary data with incomplete covariates.

Project description:Many analyses for incomplete longitudinal data are directed to examining the impact of covariates on the marginal mean responses. We consider the setting in which longitudinal responses are collected from individuals nested within clusters. We discuss methods for assessing covariate effects on the mean and association parameters when covariates are incompletely observed. Weighted first and second order estimating equations are constructed to obtain consistent estimates of mean and association parameters when covariates are missing at random. Empirical studies demonstrate that estimators from the proposed method have negligible finite sample biases in moderate samples. An application to the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) demonstrates the utility of the proposed method.

| S-EPMC3690662 | biostudies-literature

simGWAS: a fast method for simulation of large scale case-control GWAS summary statistics.

Project description:MotivationMethods for analysis of GWAS summary statistics have encouraged data sharing and democratized the analysis of different diseases. Ideal validation for such methods is application to simulated data, where some 'truth' is known. As GWAS increase in size, so does the computational complexity of such evaluations; standard practice repeatedly simulates and analyses genotype data for all individuals in an example study.ResultsWe have developed a novel method based on an alternative approach, directly simulating GWAS summary data, without individual data as an intermediate step. We mathematically derive the expected statistics for any set of causal variants and their effect sizes, conditional upon control haplotype frequencies (available from public reference datasets). Simulation of GWAS summary output can be conducted independently of sample size by simulating random variates about these expected values. Across a range of scenarios, our method, produces very similar output to that from simulating individual genotypes with a substantial gain in speed even for modest sample sizes. Fast simulation of GWAS summary statistics will enable more complete and rapid evaluation of summary statistic methods as well as opening new potential avenues of research in fine mapping and gene set enrichment analysis.Availability and implementationOur method is available under a GPL license as an R package from http://github.com/chr1swallace/simGWAS.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC6546134 | biostudies-literature

ACAT: A Fast and Powerful p Value Combination Method for Rare-Variant Analysis in Sequencing Studies.

Project description:Set-based analysis that jointly tests the association of variants in a group has emerged as a popular tool for analyzing rare and low-frequency variants in sequencing studies. The existing set-based tests can suffer significant power loss when only a small proportion of variants are causal, and their powers can be sensitive to the number, effect sizes, and effect directions of the causal variants and the choices of weights. Here we propose an aggregated Cauchy association test (ACAT), a general, powerful, and computationally efficient p value combination method for boosting power in sequencing studies. First, by combining variant-level p values, we use ACAT to construct a set-based test (ACAT-V) that is particularly powerful in the presence of only a small number of causal variants in a variant set. Second, by combining different variant-set-level p values, we use ACAT to construct an omnibus test (ACAT-O) that combines the strength of multiple complimentary set-based tests, including the burden test, sequence kernel association test (SKAT), and ACAT-V. Through analysis of extensively simulated data and the whole-genome sequencing data from the Atherosclerosis Risk in Communities (ARIC) study, we demonstrate that ACAT-V complements the SKAT and the burden test, and that ACAT-O has a substantially more robust and higher power than those of the alternative tests.

| S-EPMC6407498 | 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