![]() It is typically run from a Linux, Unix or DOS prompt by invoking the command metal. For samples that contain related individuals, a smaller ‘effective’ sample size may be used, but simulations suggest that modest changes in the effective sample size have very little impact on the final p-value. ![]() Weights are proportional to the square-root of the number of individuals examined in each sample and selected such that the squared weights sum to 1.0. ![]() Next, an overall z-statistic and p-value are then calculated from a weighted sum of the individual statistics. The z-statistic summarizes the magnitude and the direction of effect relative to the reference allele and all studies are aligned to the same reference allele. The process is actually quite simple! First, for each marker, a reference allele is selected and a z-statistic characterizing the evidence for association is calculated. One of the most common questions we receive is about the approach used by METAL to carry out a meta-analysis using p-values as input. Meta-analysis results in little or no loss of efficiency compared to analysis of a combined dataset including data from all individual studies. It is especially appropriate when data from the individual studies cannot be analyzed together because of differences in ethnicity, phenotype distribution, gender or constraints in sharing of individual level data imposed. METAL analysis is a convenient alternative to a direct analysis of merged data from multiple studies. METAL can combine either (a) test statistics and standard errors or (b) p-values across studies (taking sample size and direction of effect into account). METAL is a tool for meta-analysis genomewide association scans. Since then, it has become quite a popular tool for the analysis of genomewide association scans. The first version was developed in 2007 and was used for the analyses presented in Sanna et al (2008) and Willer et al (2008). METAL was developed by Goncalo Abecasis, Yun Li and Cristen Willer ( manuscript available here). There are a few pages in this Wiki that may be useful to METAL users. 7 Example: A METAL Meta-Analysis Script.5.4 Specifying Weights in P-value Based Analysis.
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