Instructions for the use of the FP test

Jurg Ott / 20 Dec 2012
Institute of Psychology, CAS, Beijing
Rockefeller University, New York

Graph of F=0The 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.


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