11.2 Sample parameter files for lm_lods, lm_markers, lm_bayes and lm_schnell

There are three example parameter files in the `Lodscores' subdirectory: `ped73_ge.par', `ped73_ph.par' and `ped73_qu.par'. These files are examples of how to analyze genotypic, discrete, and quantitative traits, respectively. Each of these files is written for use with lm_markers since it is our preferred program and it can analyze genotypic, discrete, and quantitative traits. The programs lm_lods, lm_bayes, and lm_schnell each require slight modifications to the parameter files, and may be limited in the trait data types they can handle. These modifications are included in each of the parameter files (see commenting).

The three parameter files share the following statements:

input pedigree file '../ped73.ped' input seed file '../sampler.seed' output overwrite seed file '../sampler.seed' input marker data file '../ped73.marker.missing' select all markers traits 1 map trait 1 all interval proportions 0.3 0.7 map trait 1 external recomb fracts 0.05 0.15 0.3 0.4 0.45 set trait 1 freqs 0.5 0.5 sample by scan set burn-in iterations 150 set L-sampler probability 0.2 set MC iterations 3000 check progress MC iterations 1000

The pedigree file specified by the `input pedigree file' statement can contain multiple traits. As discussed in previous sections, the marker map, allele frequencies and genotypes can be contained in the parameter file or in a separate file specified by the `input marker data file' statement like in the example above.

The two `map trait' statements give trait locus positions at which the LOD scores should be calculated. When the trait locus is located between two markers, the trail position is specified in terms of the proportional genetic distance between the two markers (this option makes handling gender-specific maps easy). In this example, the trait positions are specified to be at 30 and 70 percent of the interval. The second `map trait' statement allows trial trait positions located before the first marker or after the last marker to be specified; the postitions are specified explicitly in terms of recombination fractions with the nearest marker locus. Note that an external recombination fraction of 0.5 is not necessary since the likelihood of an unlinked trait locus is always used as a reference when computing the LOD scores.

The `set trait ... freqs' statement specifies allele frequencies at the trait locus. If the allele frequencies sum to less than 1, a warning message will be issued:

Sum of allele frequencies is not in range .9999, 1.0001 (W)

If the allele frequencies sum to above 1.0001, the program quits and generates an error message.

The final five statements give MCMC specifications. The `sample by scan' statement instructs the program to update all the meiosis indicators, S, at each iteration, in an order determined by random permutation. The alternative `sample by step' updates only one locus (L-sampler) or only one meiosis (M-sampler) in each iteration. In the `set burn-in iterations' statement, 100 burn-in iterations, with an unlinked trait, are requested. The L-sampler probability is set at 20 percent, which seems to be a good choice. For a detailed discussion of effects of varying L- to M-sampler ratio, see section 10.6 in Thompson (2000). The next statement requests 3000 MCMC iterations per test position of the trait locus. This is for demonstration purposes only. For real data analysis, use longer runs, on the order of 10^5 iterations per test position. The last statement tells the program to check the progress every 1000 iterations.

Specifying Trait Data Type

Trait data type is set by using the `set trait data' statement. Recall that the `input pedigree record trait' statement must be used to specify which column in the file is to be used as the trait value (see Pedigree file description statements). The three trait data types discussed in this example are implemented by including the following statements in the parameter file discussed above.

`ped73_ge.par' specifies a genotypic trait with the following statements:

set trait data genotypic input pedigree record trait 1 integer 3

`ped73_ph.par' specifies a phenotypic trait with the following statements:

set trait data discrete input pedigree record trait 1 integer 3 set incomplete penetrance 0.05 0.6 0.95

Recall that for discrete data, one must specify the penetrances see Autozyg computational parameters.

`ped73_qu.par' specifies a quantitative trait with the following statements:

set trait data quantitative input pedigree record trait 1 real 1 set trait 1 genotype mean 90.0 100.0 110.0 set trait 1 residual variance 25.0

When using a quantitative trait, genotypic means and residual variance must be specified. Additive variance may be needed to run lm_schnell and can be specified with the statement `set trait ... additive variance'. The default value is zero. Note that the `set peeling by component' statement can be used with lm_markers to compute LOD scores for each component separately, as well as jointly over all components; see the parameter file `ped73_qu.par' for this option.

The parameter files `ped73_ge.par' and `ped73_ph.par' may be used with lm_bayes, since the program works for genotypic and discrete traits.

With lm_lods and lm_schnell, MCMC is performed at each position, and so the number of MC iterations needed is less.

Below is a summary of the trait data types accepted for each program:

	Genotypic ped73_ge.par	Phenotypic ped73_ph.par	Quantitative ped73_qu.par	Notes
lm_markers	Yes	Yes	Yes
lm_bayes	Yes	Yes	No
lm_schnell	No	No	Yes	Less MC Iterations Required
lm_lods	Yes	Yes	No	Less MC Iterations Required