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| == 4. Run EPACTS association pipeline == | | == 4. Run EPACTS association pipeline == |
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− | The basic EPACTS command for single variant tests is: | + | There are three separate association analyses to be completed: |
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| + | {| width="1500" border="1" align="left" cellpadding="1" cellspacing="1" |
| + | |- |
| + | ! scope="col" | Association Analysis |
| + | ! scope="col" | Statistical Test |
| + | ! scope="col" | Subset of SNPs |
| + | ! scope="col" | Output File Type |
| + | ! scope="col" | Output Filename Format |
| + | |- |
| + | | A. Typical DIAGRAM analysis using existing association pipeline |
| + | | Wald or likelihood ratio |
| + | | All SNPs with min MAC >= 1 |
| + | | Custom file based on DIAGRAM format |
| + | | DIAGRAMv4_QQQ_XXX_1000G_KKK_YYY_ZZZ.txt |
| + | |- |
| + | | B. Analysis of all SNPs using logistic regression score test |
| + | | Score test |
| + | | All SNPs with min MAC >= 1 |
| + | | EPACTS output file |
| + | | DIAGRAMv4_QQQ_XXX_1000G_KKK_SCR_YYY_ZZZ.epacts |
| + | |- |
| + | | C. Analysis of low frequency variants using Firth bias-corrected logistic regression |
| + | | Firth bias-corrected |
| + | | SNPs with 200 >= MAC >= 1 |
| + | | EPACTS output file |
| + | | DIAGRAMv4_QQQ_XXX_1000G_KKK_FIR_YYY_ZZZ.epacts |
| + | |} |
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| + | === A. Typical DIAGRAM analysis using existing association pipeline<br> === |
| + | |
| + | This is the typical DIAGRAM analysis using your current association pipeline and software. Please follow the format here '''[INSERT PROTOCOL]'''. |
| + | |
| + | === B. Analysis of all SNPs using logistic regression score test === |
| + | |
| + | The score test has well-controlled type I error rate and good power for meta-analysis of balanced (equal numbers of cases and controls) studies. It is also very computationally efficient. Please run the score test using the EPACTS software. |
| + | |
| + | The EPACTS command for the score test analysis of all variants is: |
| <pre>epacts2.1/epacts single -vcf [INPUT VCF FILENAME] -ped [INPUT PED FILENAME] -out [OUTPUT FILENAME PREFIX] \ | | <pre>epacts2.1/epacts single -vcf [INPUT VCF FILENAME] -ped [INPUT PED FILENAME] -out [OUTPUT FILENAME PREFIX] \ |
| -test b.score -pheno DISEASE -cov AGE -sepchr -anno -min-mac 1 -run 10 | | -test b.score -pheno DISEASE -cov AGE -sepchr -anno -min-mac 1 -run 10 |
| </pre> | | </pre> |
− | This command will run single variant analysis using the score test logistic regression on the DISEASE phenotype adjusting for AGE. The VCF files are separated by chromosomes (option -sepchr). All variants with at least one minor allele count will be analyzed (option -min-mac 1). It will annotate results by functional category (option -anno) and run the analysis on 10 parallel CPUs (option -run 10). | + | This command will run single variant analysis using the score test logistic regression on the DISEASE phenotype adjusting for AGE. Add the relevant additional covariates with additional "-cov" options. This assumes that the VCF files are separated by chromosomes (option -sepchr). All variants with at least one minor allele count will be analyzed (option -min-mac 1). It will annotate results by functional category (option -anno) and run the analysis on 10 parallel CPUs (option -run 10). |
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− | To run the Firth test as well, use: | + | === C. Analysis of low frequency variants using Firth bias-corrected logistic regression === |
| + | |
| + | The Firth bias-corrected test has well-controlled type I error rate and good power for analysis of balanced and unbalanced studies. However, it is more computationally intensive. We only run Firth on the subset of variants with 1<= MAC <= 200. |
| + | |
| + | To run the Firth test using the EPACTS software: |
| <pre>epacts2.1/epacts single -vcf [INPUT VCF FILENAME] -ped [INPUT PED FILENAME] -out [OUTPUT FILENAME PREFIX] \ | | <pre>epacts2.1/epacts single -vcf [INPUT VCF FILENAME] -ped [INPUT PED FILENAME] -out [OUTPUT FILENAME PREFIX] \ |
− | -test b.firth -pheno DISEASE -cov AGE -sepchr -anno -min-mac 1 -run 10 | + | -test b.firth -pheno DISEASE -cov AGE -sepchr -anno -min-mac 1 -max-mac 200 -run 10 |
| </pre> | | </pre> |
− | Note that the Firth bias-corrected test is more computationally intensive than the score test.
| + | |
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| For detailed description of options, use: | | For detailed description of options, use: |
| <pre>epacts2.1/epacts single -man | | <pre>epacts2.1/epacts single -man |
− | </pre> | + | </pre> |
| + | |
| == 5. Report association results in appropriate format<br> == | | == 5. Report association results in appropriate format<br> == |
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