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 q_{1} =
frequency of AA
genotypes, and q_{3} = 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 q_{1} and q_{3},
and biologically reasonable values, *F* > 0,
correspond to
2/3 of the unrestricted parameter space (q_{1}, q_{3}).
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