Interactions for pairs of DNA variants
Jurg Ott, Rockefeller University, New York
10 Feb 2020
These analysis programs
refer to statistical interaction between a pair
of variants, where one variant is from one gene and the other variant
from another gene. There are a number of genes, and variants within
a gene, and we want to evaluate all possible pairs of genes and pairs
of variants under
the given restrictions.
In our publication , there are 5 genes and, thus, 10 gene pairs.
Each gene had a varying number of SNPs leading to a total of 840,899
pairs of SNPs. Here, we work with a sample dataset. Originally, this
was a case-control dataset for schizophrenia  with 255,053
genome-wide SNPs. We used the same genes as in our
publication  even though these genes refer to hyperlipidemia, but we
simply wanted to prepare a toy dataset. Here is the resulting data
layout, with a total number of 28 SNPs:
of positions in toy dataset
|number of SNPs
|21,208,207 - 21,274,333
|11,195,179 - 11,237,675
|45,403,173 - 45,418,176
To run the toy dataset with our analysis program, GenePairsPerm, we
need to prepare a parameter file, genepairs.param, which will be read
by the program. An example parameter file is as follows:
schizoT2genes Input file names, schizoT2genes.tped and schizoT2genes.tfam
To run the GenePairsPerm program you may double-click on its name or,
preferably, run it in a Windows or Linux command window (terminal).
Upon program termination, you will see various files as follows:
LDLRAP1 1 3
PCSK9 4 8
APOB 9 13
LDLR 14 24
APOE 25 28 need blank line below
1 Test number, 1 = trend test, 2 = geno test
10000 Number of permutations
0 min. chisquare for output
0.5 empty, value of empty cells in contingency tables, might be 0
GPair1Test1.out ... GPair10Test1.out: For a given gene pair, these
files list results for each SNP pair analyzed, where Test1 refers to
the trend test and Test2 would refer to the genotype test.
gpairsLimitItest1.txt: This file contains all null data but only for
chisqD exceeding the minimum chisquare given in the parameter file
permgenepairsItest1.log: This log file presents information on the current run.
permgenepairsItest1.log.null: This file contains all null data; it may be used to establish significance limits for chi-square.
seed.txt contains a seed for the random permutation analysis and is updated after every run.
 Okazaki A, et al: Main and interaction effects between variants
underlying hyperlipidemia (in preparation)
 Ott J, Macciardi F, Shen Y, Carta MG, Murru A, Triunfo R, Robledo
R, Rinaldi A, Contu L, Siniscalco M: Pilot study on schizophrenia in
Sardinia. Hum Hered 2010;70:92-96