6 Using SAMPLE

SAMPLE generates (multiple) haplotype or genotype samples from a FREGENE output population. Either a case-control sample, random sample with a continuous phenotype or a random sample with no phenotype can be generated. The number of cases must be set zero if a continuous phenotype or random sample is required. Otherwise, cases/control status is assigned according to a disease model that is multiplicative over genotypes at each causal SNP, and also multiplicative over SNPs if the number causal SNPs selected is greater than 1. To generate individuals with a continuous phenotype the -sigma option must be selected, this parameter specifies the phenotypic standard deviation. The heritability of each SNP must be specified from which the regression coefficient are calculated;

$$\beta=\sqrt{\frac{\sigma^2h^2}{2f(1-f)(1-h^2)}}$$

where $f$ is the MAF, $h^2$ is the user specified heritability and the genotypes are coded as (-1, 0, 1). Thus, each individuals phenotype is sampled from the following Gaussian distribution

$$x\sim$$N$$\left(\sum\beta_i x_i, \sigma^2\right)$$

where the $x_i$ 's are the genotypes at the selected causal SNPs. Causal SNPs are selected at random within allele frequency bands specified by the -f option.

All options are set on the command line.

• -i file_name (required):
  Input file, usually the output file of a FREGENE run ($e.g.$ data/rin_example.xml).
• -og file_name option:
  Records genotypes of sampled individuals. Case control status is first entry on each line, followed by genotypes coded as 0, 1, 2.
• -oh file_name option:
  Records haplotypes of sampled individuals in file_name, each haplotype on a separate line. For both haplotypes of an individual, the 1st column is its case/control status then alleles are recorded as 0 (major) or 1 (minor). Either og or oh must be specified; if both are specified then both output files are generated.
• -scan file_name option:
  File containing list of locations of SNPs output to the genotype and/or haplotype files.
• -min int option:
  Specifies the minimum MAF of loci that are output. If neither this option or -scan are selected all polymorphisms are written to file the genotype and/or haplotype files.
• -chromolength float option:
  This option takes as an argument a chromosome length in Mb; the returned chromosomes are then restricted to be of this length.
• -LD file_name option:
  Argument specifying output file that lists all pairs of SNPs within 200kb of each other and their pairwise $r^2$ value. (see ./data_sample/LD_example.txt).
• -sd int option:
  Seed for random number generator.
• -controls int option:
  Number of controls to sample.
• -samples int option:
  Specifies the number of case-control, or just control, samples, default = 1.

To generate a phenotype, either binary or continous, the following options must be specified

• -cases int option, only required for a binary phenotype:
  This options specifies that the phenotype is binary and sets the number of cases to sample, default = 0.
• -sigma float option, only required for a continuous phenotype:
  This options specifies that the phenotype is continuous and sets the phenotypic standard deviation.
• -prev float option, only required for a binary phenotype:
  Disease prevalence, value between 0 and 1.
• -snps int option:
  Number of causal SNPs ($i.e.$ that influence phenotype), default = 0.
• -length int option:
  Size (in Mb) of the chromosome the user wants to generate haplotype data for. If this option is not chosen, this chromosome length considered is equal to the one in FREGENE output file.
• -f float$_1$ ... float$_{2k}$ option:
  Two arguments per causal SNP, specifying its minimum and maximum allele frequencies.
• -rr float$_1$ ... float$_k$ option:
  One argument per causal SNP, if binary phenotype is specified the option specifies the risk ratio for both the heterozygote relative to the common homozygote, and also the rare homozygote relative to the heterozygote. If a continuous phenotype is specified the option specifies the heritability attributed to each SNP. SNP order should be the same as for -f.
• -log file_name (required):
  Records disease model details of each sampled file (see data_sample/log_sample_example*.dat).