Changes

== Approach ==

== Approach ==

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. The process is actually quite simple! First, for each marker, an arbitrary reference allele is selected and a z-statistic characterizing the evidence for association is calculated. The z-statistic summarizes the magnitude and the direction of effect relative to the reference allele.  Next, an overall z-statistic and p-value are then calculated from a weighted sum of the individual statistics. 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. 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.

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. 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. 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.  Next, an overall z-statistic and p-value are then calculated from a weighted sum of the individual statistics. 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. 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.

== Basic Usage Instructions ==

== Basic Usage Instructions ==