Changes

Gene-based tests can be conducted centrally by Scott using output from Rare-Metal-Worker.

Gene-based tests can be conducted centrally by Scott using output from Rare-Metal-Worker.

We will implement two burden tests.  First, a Variable Threshold Combined Multivariate and Collapsing count method, where the number of rare alleles is counted in each gene, then the gene is tested for association.  Second, we will use SKAT for all rare variants (MAF < .05) within a gene.  SKAT allows for variants with opposite directions of effect within the same gene, whereas the variable threshold combined multivariate and collapsing method does not.  

We will implement three burden tests.  First, a Variable Threshold Combined Multivariate and Collapsing count method (described in this publication [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032073/ | VTCMC]], where the number of rare alleles is counted in each gene, then the gene is tested for association. The threshold for what variants are considered "rare" (MAF < .05? MAF < .01?) is set adaptively such that the result minimizes the p-value obtained.  Second, we will use SKAT for all rare variants (MAF < .05) within a gene.  SKAT allows for variants with opposite directions of effect within the same gene, whereas the variable threshold combined multivariate and collapsing method does not.  

Other Analysis Considerations

Other Analysis Considerations