Composite Genotype Example

The Composite Genotype example allows a user to examine the joint inheritance of two or more markers, without considering phase of the data. A haplotype frequency file is required for this analysis. We have also included quantitative data in this analysis. If you have problems opening a file, at the error page try using toolbar View, Source or click on Page, View Source to view the file.

Files required :

GenotypeData.dat - Linkage pre-makeped pedigree file with a header lineTrait.dat - Trait / Covariate data filehapMCCompGenotype.rgen - .rgen Parameter File

Output file :

hapMCCompGenotype.report

To run this analysis:

java -jar Genie.jar hapMC hapMCCompGenotype.rgen

GenotypeData.datThe example Genotype Data file is composed of 16 three generation families. Each individual has information on two markers.

Trait.datThe quantitative test requires a quantitative trait file. It contains the trait and covariate information for each individual.

hapMCCompGenotype.rgenPlease refer to the .rgen Parameter File Description for a point-by-point description of each section of the ‘.rgen’ file. Here we highlight a few of the features of the hapMCCompGenotype.rgen file that a user may wish to alter when running an analysis with more than two loci.

  1. nsims=”2000”. The number of simulations is 2,000. A user may wish to increase or decrease this value.
  2. In the locus section, we list two loci to be analyzed, and they have the names SNP1 and SNP2.Loci are defined, as is the distance (‘dist’) between the loci. The ‘dist’ is defined as the distance between the marker and the proceeding marker. If the ‘dist’ is listed as a value <=0.5, it is assumed to be a recombination fraction. If the ‘dist’ is listed as a value >0.5 it is assumed to a value in centiMorgans (cM). The default value for ‘dist’ is 0.5, assuming linkage equilibrium between markers.
  3. The [“top-sample”] option of ‘all’ or ‘founder’ is for allele frequency estimation. For hapMC2 analyses, the [“top-sample”] option is ignored.
  4. The statistics of interest listed under ‘optional modules’ for this analysis are the chi-square, chi-square trend, odds ratio, and the difference in means quantitative statistics using quantitative data from the Trait.dat file and the first column (covar1) of data following the kindred and individual identifier columns.
  5. In the first cctable analysis, SNP1 and SNP2 are tested jointly, both in a state of dominant inheritance. We did not list specific loci (eg., loci=”1”) to test and thus all markers defined in the locus section will be tested. We point out to users that within a defined block, each line listed is joined together by an ‘AND’ statement. Between blocks are ‘OR’ statements. Thus in the first block, the first line requires that the first locus (SNP1) be a ‘1/1’ genotype AND the second line states that the second locus (SNP2) can be ‘any’ (./.) genotype. Also within wt=0, we define the scenario where the first locus (SNP1) can be ‘any’ (./.) genotype, but the second locus (SNP2) is required to have the 1/1 genotype. Thus for wt=0, we require that either SNP1 or SNP2 or both have a 1/1 genotype. The comparison group (wt=1), requires a ‘2’ in at least one position for both the first (SNP1) and second (SNP2) loci. The ‘OR’ statement (i.e., ‘|’) allows for unphased genotype data. All statistics in the above ‘ccstat’ list will be run as no ‘stats’ are defined.
  6. In the second cctable analysis, SNP1 and SNP2 are tested jointly, both in a state of recessive inheritance. Under wt=0, we require the first locus (SNP1) to have a ‘1’ in either the first or second position of their genotype. Thus, the SNP1 genotype could be ‘1/1’, ‘1/2’, or ‘2/1’. Any genotype (./.) is permissible for SNP2. Also under wt=0, SNP1 could be any genotype, but a ‘1’ is required for SNP2. We then define wt=1 as requiring SNP1 and SNP2 to both have the ‘2/2’ genotype.
  7. Other combinations of the joint inheritance of SNP1 and SNP2 may be compared. We illustrate in cctable 3 the joint inheritance of a dominant mode of inheritance for SNP1 and a recessive mode for SNP2. In cctable 4, we model the joint inheritance of recessive mode of inheritance for SNP1 and a dominant mode for SNP2.

hapMCCompGenotype.report output file

  1. The output file begins with a header stating the date and time the file was run, parameters that were defined in the ‘.rgen’ file including statistics, loci, number of simulations, etc.
  2. Each separate cctable defined in the ‘.rgen’ parameter file creates a separate analysis section in the output. For Analysis1, we point out that Loci is defined as ‘ALL MARKERS’ as we did not define a specific marker to analyze in the CompositeGenotype.rgen file. Our defined Model is ‘Dom-Dom’ (SNP1 and SNP2 both in a state of a dominant mode of inheritance), and the Type of data is ‘genotype’ data. The odds ratio statistic is listed as a ‘-‘ as one of the cells in the contingency table has ‘0’ value.
  3. For Analysis2 where SNP1 and SNP2 were set up to both be in a recessive mode of inheritance, we note that the number of statistics calculated is less than the number of simulations (i.e., 0 / 2000 for chi-square and chi-square trend statistics, 1063 / 2000 for the odds ratio, and 316 / 2000 for the quantitative statistic). Upon examination of the contingency table we see that there were ‘0’ cases and ‘0’ controls in the observed data that had both a 2/2 genotype for SNP1 and a 2/2 genotype for SNP2. Due to ‘sparse’ data, no statistics could be calculated.
  4. Results are also shown for the combined dominant (SNP1) - recessive (SNP2) model as well as for the recessive (SNP1) - dominant (SNP2) model.

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