Changes

There are a number of useful commands related to the analysis that are typically set early in the analysis.  For example, the user can choose to weight studies in the meta-analysis using the inverse of the standard error, or the square root of the sample size.  These are proportionate.  Users should be cautious when weighting based on standard error that the beta and standard error are in the same units for all studies (i.e. same trait and same transformation applied to the trait).  The default weighting scheme is SAMPLESIZE.

There are a number of useful commands related to the analysis that are typically set early in the analysis.  For example, the user can choose to weight studies in the meta-analysis using the inverse of the standard error, or the square root of the sample size.  These are proportionate.  Users should be cautious when weighting based on standard error that the beta and standard error are in the same units for all studies (i.e. same trait and same transformation applied to the trait).  The default weighting scheme is SAMPLESIZE.

SCHEME STDERR

SCHEME STDERR

METAL has an option to perform genomic control correction to all input files.  METAL will estimate the inflation of the test statistic by comparing the median test statistic to that expected by chance, and then apply the genomic control correction to the p-values (for SAMPLESIZE weighted meta-analysis), or the standard error (for STDERR weighted meta-analysis).  This should only be applied to files with whole genome data (i.e. should not be used for cohorts that only performed genotyping of replication SNPs).  Genomic control can be turned off and on for different input files.  We recommend applying genomic control correction to all input files, and also to the final output by loading the initial results file into METAL to perform genomic control correction on the final results.

METAL has an option to perform genomic control correction to all input files.  METAL will estimate the inflation of the test statistic by comparing the median test statistic to that expected by chance, and then apply the genomic control correction to the p-values (for SAMPLESIZE weighted meta-analysis), or the standard error (for STDERR weighted meta-analysis).  This should only be applied to files with whole genome data (i.e. should not be used for cohorts that only performed genotyping of replication SNPs).  Genomic control can be turned off and on for different input files.  We recommend applying genomic control correction to all input files, and also to the final output by loading the initial results file into METAL to perform genomic control correction on the final results.

GENOMICCONTROL ON

 

'''GENOMICCONTROL ON'''

METAL will optionally keep track of the effect allele frequency across all files and provide the mean, minimum and maximum.  This can be quite useful to determine whether the frequencies are similar across different cohorts after METAL performs all strand alignment.  METAL requires all input files to have an allele frequency column when this feature is turned on.

METAL will optionally keep track of the effect allele frequency across all files and provide the mean, minimum and maximum.  This can be quite useful to determine whether the frequencies are similar across different cohorts after METAL performs all strand alignment.  METAL requires all input files to have an allele frequency column when this feature is turned on.

AVERAGEFREQ ON

 

MINMAXFREQ ON

'''AVERAGEFREQ ON<br>'''

'''MINMAXFREQ ON'''

Then, for each individual file, the following command will be used;

Then, for each individual file, the following command will be used;

FREQLABEL EffectAlleleFrequencyColumnHeading

FREQLABEL EffectAlleleFrequencyColumnHeading

CUSTOMVARIABLE TotalSampleSize

CUSTOMVARIABLE TotalSampleSize

For each individual input file;

For each individual input file;

LABEL TotalSampleSize as N

LABEL TotalSampleSize as N

USESTRAND ON

USESTRAND ON

For each individual file;

For each individual file;

STRAND StrandColumnHeading

STRAND StrandColumnHeading