Instructions for the use of the FP test

Jurg Ott / 20 Dec 2012
Institute of Psychology, CAS, Beijing
Rockefeller University, New York The theory of this association test may be found in the manuscript listed below (Zhang et al 2008). The essence of this approach is a feature analogous to Holman's triangle. Consider a 2 x 3 table with rows corresponding to cases and controls, and columns representing the three genotypes of a SNP, AA, AB, and BB. The table body contains numbers of individuals. A chi-square association test of these data has 2 df, which may be represented by q1 = frequency of AA genotypes, and q3 = frequency of BB genotypes. For the FP test, the 2 df are re-formulated in terms of SNP allele frequency p and inbreeding coefficient F. The equation F = 0 is a curved line in the plane spanned by q1 and q3, and biologically reasonable values, F > 0, correspond to 2/3 of the unrestricted parameter space (q1, q3). It is this restriction that makes the FP test more powerful than the 2 df chi-square test, particularly under recessive inheritance and when cases show more homozygotes than expected under HWE.

Download the program package and move its contents into a folder. Preferably, run the FPtest program in a Windows command window (CMD), or double-click on FPtest (FPtest.exe).

The program will ask you to furnish, for a given SNP, numbers of individuals with genotypes AA, AB, and BB, both for cases and for controls. It will then compute p-values via permutation samples, with the observed data being counted as a null dataset. With n = 1,000,000 permutations (default), the smallest p-value that can be obtained is 1/(n + 1) = 10-6, where n is the number of permutations performed. The program will write output to a file called FPtestout.txt.

Permutation analysis will require a seed for the random number generator. The program will create this seed based on the system clock unless you provide a file called seed.txt containing a positive integer number. The FPtest has also been implemented in our sumstat program package.

Linux users may want to compile the source code with the FPC compiler.

A sample dataset, FPdataNielsen.txt, is provided, which has been taken from Table 2 in Nielsen et al (2008). You may run this dataset by typing FPtest <FPdataNilsen.txt.

References

Nielsen DA, Ji F, Yuferov V, Ho A, Chen A, Levran O, Ott J, Kreek MJ: Genotype patterns that contribute to increased risk for or protection from developing heroin addiction. Mol Psychiatry 2008;13:417-428

Zhang Q, Wang S, Ott J: Combining identity by descent and association in genetic case-control studies. BMC Genet 2008;9:42