5. Haplotype Association Tests

Though chi-square p-values are generated live in the Data Console of the LD Plot you may want to perform more robust association tests. Golden Helix SVS provides two overall methods for association testing – per haplotype and per block tests.

A. Performing Per Haplotype Association Tests

• Open the –log10 P + LD plot and select (click on) Block 2.
• Click the Subset Markers button in the Item tab.

This creates a subset spreadsheet (HapMap Phenotype + 500K Genotypes – Block 2 Subset) of only those markers in the block. Phenotype information is also represented.

• From HapMap Phenotype + 500K Genotypes – Block 2 Subset, select Analysis >Haplotype Association Tests.

The Haplotype Association Tests window appears with a number of parameter settings. Set the parameters as follows:

• In this case we are treating all markers in the subset spreadsheet as a single block. Thus under Haplotype Block Definition, select Use all markers as single block.
• Under Haplotype Association Tests, select Calculate per haplotype.
• Under Tests select Chi-squared test and Odds ratio with 95% CI.
• Under Multiple Testing Correction check only Bonferroni adjustment (on N covariates).
• Under Additional Outputs, check Haplotype frequencies and Output data for P-P/Q-Q plots.
• Click Run to finish.

A single spreadsheet (Haplotype Association Tests (Per Haplotype)) is produced with a row for each haplotype and a column for each test statistic selected. Notice again that only the first marker of the block is represented in the row label column.

B. Performing Per Block Haplotype Association Tests

Another, perhaps more informative test of association is a per block test where a 2 X N chi-square table is used with N = the number of haplotypes represented.

Figure 6a. Per-haplotype association test results.

• Again, open HapMap Phenotype + 500K Genotypes – Block 2 Subset, and select Analysis >Haplotype Association Tests.
• Leave all the parameters the same except this time select Calculate per block under Haplotype Association Tests.
• Click Run to finish.

A new spreadsheet is created (Haplotype Association Tests (Per Block)) with a single row of data representing per block association results.