Gwama software for genome-wide association meta-analysis meaning

Moreover, stata implementations for the max, min2 and gms approach are given for the first time. Secure quality control for metaanalysis of genomewide. Meta is a program for the meta analysis of genome wide association studies. It allows for incompatibility between phenotype units. Metaanalysis of genomewide association data and largescale. We have developed flexible, opensource software for the metaanalysis of genomewide association studies. Performs meta analysis of genome wide association studies gwass. Gwama tutorial university of tartu institute of genomics. We aimed to increase our understanding of the genetic determinants of vitamin d levels by undertaking a largescale genomewide association study gwas of serum 25 hydroxyvitamin d 25ohd. Fixed effects model fe, random effects model re, han and eskins random effects model re2 and binary effects model be. We performed the genomewide metaanalysis using gwama v2. Method can use summarylevel statistics from a meta analysis of genome wide association studies gwas and ld information from a reference panel computationally fast avoids having to go back to individuals cohorts for iterative rounds of conditional analysis.

We introduce multitrait analysis of gwas mtag, a method for joint analysis of summary statistics from genome wide association studies gwas of different traits, possibly from overlapping samples. Zeng department of biostatistics, university of north carolina, chapel hill, north carolina to identify genetic variants with modest effects on complex human diseases, a growing number of networks or consortia. Statistical analysis of genomewide association gwas data. Abstract metaanalysis of genomewide association studies gwass has become. Code for multivariate genome wide association meta analysis 84 commits 1. Dear all, i would like to run the basic command for the meta analysis as follow. Studies gwas genomewide association handson tutorial. With relatively modest sample and effect sizes, a true association between genotype and phenotype may never meet genomewide statistical significance p association between the 2q33. Candidate gene and genome wide association studies gwas have sought genes, chromosomal regions and allelic variants likely to contribute to susceptibility to drug addiction.

Of note, in both gwass, 25ohd levels were first logtransformed and then standardized to a mean of 0 and a standard deviation of 1. Further studies are needed to confirm the association between hla typing or rs2856830. Ioannidis 2,3 abstract meta analysis of genome wide association studies gwass has. Table 2 comparison of metaanalysis software packages. Randomeffects model aimed at discovering associations in. We conducted a genomewide association metaanalysis of 4,604 endometriosis cases and 9,393 controls of japanese1 and european2 ancestry. We then combined the summarylevel results of the two gwass in an inverse variance weighted fixed effects metaanalysis, using the gwama 54 software. If enabled, metal checks if chromosome and position of a variant match across studies. Genomewide association metaanalysis gwama is a statistical tool that aims to synthesize results from multiple independent studies to increase the statistical power and reduce falsepositive. Software with source files, documentation and example data files are freely. Granvil is an implementation of a burden test to perform rarevariant analysis of binary or quantitative phenotypes with functional units. With relatively modest sample and effect sizes, a true association between genotype and phenotype may never meet genomewide statistical significance p genome wide association studies. In genetics, a genome wide association study gwa study, or gwas, also known as whole genome association study wga study, or wgas, is an observational study of a genome wide set of genetic variants in different individuals to see if any variant is associated with a trait. Performs metaanalysis of summary statistics generated from genomewide.

Particularly, the program is able to work seamlessly with the output of snptest. Genomewide association meta analysis software performs metaanalysis of the results of gwa studies of binary or quantitative phenotypes. Not surprisingly, studies differ in design, sample collection, genotyping platforms, association analysis methods, and so forth. Here we develop a multisite adaptable protocol using freely available and common neuroimaging software for voxelwise volumetric analysis by tensorbasedmorphometry tbm, and we then describe genomewide association testing in the resulting data. Genetic determinants of risk in pulmonary arterial hypertension. The software is distributed with scripts that allow simple formatting of files containing the results of each association study and generate graphical summaries of genomewide metaanalysis results. Several methods and software tools have been developed for metaanalysis of gwas e. This tutorial is a learning resource that outlines the basic process and provides specific software tools for implementing a complete genome. We have developed flexible, opensource software for the meta analysis of genome wide association studies.

Metaanalysis of genomewide association studies and network. May 28, 2010 the software is distributed with scripts that allow simple formatting of files containing the results of each association study and generate graphical summaries of genomewide metaanalysis results. Hence, we performed a genomewide association metaanalysis of four studies totaling 3528 healthy individuals of european descent and for whom plasma a. Easyqc, a flexible, userfriendly software that implements this gwama qc pipeline and can accommodate additional and alternative steps. In the metaanalysis of the previous version, the ukb dataset was weighted with an incorrect sample size, overestimating it by max 22,246 5%.

Manhattan plots for horvatheaa and hannumeaa are shown in fig 4, with qq plots of the observed pvalues versus those expected shown in. Although with different strength, the association was also observed in all the different diarrhoeal outcomes investigated. Gwama genomewide association meta analysis software has been developed to perform metaanalysis of the results of gwa studies of binary or quantitative phenotypes. In genetics, a genomewide association study gwa study, or gwas, also known as whole genome association study wga study, or wgas, is an observational study of a genomewide set of genetic variants in different individuals to see if any variant is associated with a trait. These methods have been employed successfully, with hundreds of gwas metaanalyses being published panagiotou et al. Genome wide association gwa studies scan an entire species genome for association between up to millions of snps and a given trait of interest. May 28, 2010 although statistical software analysis packages incorporate routines for meta analysis, they are ill equipped to meet the challenges of the scale and complexity of data generated in genome wide association studies. Gwama can be used for analysing the results of all different genetic models multiplicative, additive, dominant, recessive. Genomewide association studies gwas have successfully identified genes associated with complex human diseases. Gwama genomewide association meta analysis software to perform metaanalysis of the results of gwa studies of binary or quantitative phenotypes. Specifically, we used a fixed effects model with inverse variance to combine the regression coefficients of. One approach to overcome this problem is to combine the results of gwa studies from closely related populations via metaanalysis, without direct exchange of genotype and phenotype data.

These gwas used data from four international casecontrol studies across 11 744 individuals with european ancestry including 2085 patients. Software tool for meta analysis of whole genome association data background genomewide association gwa studies have proved to be extremely successful. This tool converts studyspecific pvalues and direction of effect into a signed zstatistic. A list of available software for robust analysis and meta analysis of gas and gwas is also given. Metaanalysis of genomewide association studies for body. We identify 49 genomic regions at a false dicovery rate fdr genome wide association study gwas of serum 25 hydroxyvitamin d 25ohd. Correction for sample overlap in sample size weighted meta analysis developed by sebanti sengupta. Metasoft is a meta analysis software designed for performing a range of basic and advanced meta analytic methods. The gwama genomewide association metaanalysis software has been developed to perform metaanalysis of summary statistics generated from genomewide association studies of dichotomous phenotypes or quantitative traits. Metaanalyses between the qatari and uk samples were carried out using the genomewide association metaanalysis gwama software. Metaanalysis of genomewide association studies discovers. Available metaanalysis software, such as metal willer et al. Metaanalysis of genomewide association studies gwass has become a popular method for discovering genetic risk variants.

Article randomeffects model aimed at discovering associations in meta analysis of genome wide association studies buhm han1 and eleazar eskin2, meta. Software with source files, documentation and example data files are. Meta analysis methods for genome wide association studies and beyond evangelos evangelou 1 and john p. Metaanalysis and genomewide interpretation of genetic.

The gwama genomewide association metaanalysis software has. Gwama genomewide association meta analysis software performs metaanalysis of the results of gwa studies of binary or quantitative phenotypes. Meta analysis of genome wide association data can improve the power for detecting and validating such associations. Due to the limited power of smallscale genomewide association studies gwas, researchers tend to collaborate and establish a larger consortium in order to perform largescale gwas. In this study, we perform a genomewide metaanalysis of ltl by pooling densely genotyped and imputed association results across largescale europeandescent studies including up to 78,592 individuals. Here, kiel and colleagues perform a meta analysis of genome wide association studies for whole body. We identify 49 genomic regions at a false dicovery rate fdr genomewide association metaanalysis of the eight strata was performed using the gwama software. The chromosome and position fields are propagated to the meta analysis result file useful when generating manhattan or locuszoom plots. Metaanalyses of genomewide association studies gwas have proven to be. The program is designed to synthesizing the evidence from different association studies. Notably, the trait of interest can be virtually any sort of phenotype ascribed to the population, be it qualitative e. We have reran the metaanalysis and have uploaded the new summary statistics.

The genome wide association meta analysis followed by replication identified an association between rs8111874 mapping to the 19q. We used three different software tools to search for relationships. The gwama genomewide association metaanalysis software has been. Fixed and randomeffect metaanalyses are performed for both directly genotyped and imputed snps using estimates of the allelic odds ratio and 95% confidence interval for binary traits, and estimates. No efficiency gain in using individual participant data d. Genomewide association study for vitamin d levels reveals 69. To do so, we used imputed genotypes from 401,460 white british uk biobank participants with available 25ohd levels, retaining singlenucleotide polymorphisms snps with minor allele frequency maf 0. Metaanalysis of genomewide association data and largescale replication identifies additional susceptibility loci for type 2 diabetes.

Genomewide complex trait analysis gcta genomebased restricted maximum likelihood greml is a statistical method for variance component estimation in genetics which quantifies the total narrowsense additive contribution to a traits heritability of a particular subset of genetic variants typically limited to snps with maf 1%, hence terms such as chip heritabilitysnp heritability. For genomewide association testing, we used boltlmm to run an lmm. Metaanalysis methods for genomewide association studies and. Association pvalues of the discovery data ccfr and bcfr and replication data gecco were metaanalyzed using the genomewide association metaanalysis software, gwama v. Here, we performed a meta analysis of addiction candidate gene association. An updated metaanalysis including 18,019 individuals eun pyo hong 1,2,3, bong jun kim 3 and jin pyeong jeon 3,4,5, 1 molecular neurogenetics unit, center for genomic medicine, massachusetts general hospital, boston, ma 02114, usa.

Genomewide association metaanalysis of 1,447,416 markers, applying the additive model to eight casecontrol strata, identified 49 regions that contained one or more marker with p 5e5. Oct 15, 2011 classical genetic studies provide strong evidence for heritable contributions to susceptibility to developing dependence on addictive substances. Scientists aiming to undertake genome wide association studies and their meta analyses researchers analyses of data using plink software, including genetic models used for statistical analysis, covariates and adjustments, bawilling to understand better the statistical approaches and analytical procedures for the genetic association studies. Meta analysis of genome wide association studies discovers multiple loci for chronic lymphocytic leukemia sonja i. Despite the small sample size for a genome wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with lewy bodies so far.

We conducted genomewide association metaanalyses of horvatheaa and hannumeaa using,493 europeanancestry individuals aged between ten and 98 years from 12 cohorts, adjusting for sex. Leukocyte telomere length ltl is a heritable biomarker of genomic aging. Although much of the heritability remains unexplained, combining single nucleotide polymorphism snp genotypes from multiple studies for metaanalysis will increase the statistical power to identify new diseaseassociated variants. The gwama genomewide association metaanalysis software has been developed to perform metaanalysis of summary statistics generated from genome. Metaanalysis of the results from the two cohorts was performed using the gwama genomewide association metaanalysis software package a fixed effects model was applied, combining estimates of the allelic effect size and. Genomewide association analyses in 128,266 individuals.

All participating subjects were of european origin see s1 and s3 tables for details. Conclusions the gwama genomewide association metaanalysis software has been developed to perform metaanalysis of summary. Here, we overview both widely applied and newer statistical methods for. Epigenetic associations of type 2 diabetes and bmi in an. As a proof of concept, a stata program that implements the meta analysis using the mert statistic is given below. Gwama genomewide association metaanalysis performs metaanalysis of summary statistics generated from genomewide association studies of dichotomous phenotypes or quantitative traits. The genomewide association study gwas approach has been. The gwama genomewide association metaanalysis software has been developed to perform metaanalysis of summary statistics generated from genomewide association studies of dichotomous. Selection biases need to be considered as in any meta analysis. Statistical analysis of genomewide association gwas data jim stankovich menzies research institute university of tasmania j. Metaanalysis of genomewide association data and largescale replication identi.

Also, for snps that had significant p values only in males or females i. Genomewide association study for vitamin d levels reveals. Performs metaanalysis of summary statistics generated from genome wide. Metaanalysis of genomewide association studies for personality. Meta analysis in plink what to use in order to do a forest plot i am doing a meta analysis using plink. Impairment of sox17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in sox17. Tools for robust analysis and metaanalysis of genomewide association studies within the context of genomewide association studies gwas there is a variety of statistical techniques in order to conduct the analysis but for complex diseases, the underlying genetic model is usually unknown.

Genomewide association metaanalysis identifies new. To further understand the genetic susceptibility for cll and identify common loci. This is the first study to report that common genetic variation at loci in an enhancer near sox17 and in hladpa1dpb1 is associated with pulmonary arterial hypertension. Pulmonary arterial hypertension was defined by haemodynamic criteria. Tools for robust analysis and metaanalysis of genome. This resulted in a slight underestimate of effect sizes and slightly less significant pvalues in the order of the 9th decimal. Gwama is a software tool for metaanalysis of genomewide association studies of binary or quantitative traits. We did two separate genomewide association studies gwas and a metaanalysis of pulmonary arterial hypertension. In this study, we perform a genome wide meta analysis of ltl by pooling densely genotyped and imputed association results across largescale europeandescent studies including up to 78,592 individuals. Genomewide association analysis in humans links nucleotide. Meta is designed to summarize the evidence from different association studies.

Multitrait analysis of genomewide association summary. Metaanalysis of genomewide association studies and. A metaanalysis of genomewide association studies of. Genetic determinants of risk in pulmonary arterial. Gwama genomewide association meta analysis software to perform metaanalysis of the results. Metaanalysis methods for genomewide association studies.

We have developed the gwama genomewide association meta analysis software to perform metaanalysis of the results of gwa studies of binary or quantitative. These data show that common genetic variability has a role in the disease. We did two genomewide association studies and a metaanalysis on pulmonary arterial hypertension. Large metaanalysis of genomewide association studies. Although statistical software analysis packages incorporate routines for metaanalysis, they are ill equipped to meet the challenges of the scale and complexity of data generated in genomewide association studies. Education software downloads metastat by ericae and many more programs are available for instant and free download.