R: Sequential Haplotype Scan Association Analysis for...

seqhap {haplo.stats} | R Documentation

## Sequential Haplotype Scan Association Analysis for Case-Control Data

### Description

Seqhap implements sequential haplotype scan methods to perform association analyses for case-control data. When evaluating each locus, loci that contribute additional information to haplotype associations with disease status will be added sequentially. This conditional evaluation is based on the Mantel-Haenszel (MH) test. Two sequential methods are provided, a sequential haplotype method and a sequential summary method, as well as results based on the traditional single-locus method. Currently, seqhap only works with bialleleic loci (single nucleotide polymorphisms, or SNPs) and binary traits.

### Usage

    seqhap(y, geno, pos, locus.label=NA, weight=NULL,
           mh.threshold=3.84, r2.threshold=0.95, haplo.freq.min=0.005,
           miss.val=c(0, NA), sim.control=score.sim.control(),
           control=haplo.em.control())
    ## S3 method for class 'seqhap'
    print(x, digits=max(options()$digits-2, 5), ...)

### Arguments

`y` | vector of binary response (1=case, 0=control). The length is equal to the number of rows in geno.
`geno` | matrix of alleles, such that each locus has a pair of adjacent columns of alleles, and the order of columns corresponds to the order of loci on a chromosome. If there are K loci, then ncol(geno)=2*K. Rows represent the alleles for each subject. Currently, only bi-allelic loci (SNPs) are allowed.
`pos` | vector of physical positions (or relative physical positions) for loci. If there are K loci, length(pos)=K. The scale (in kb, bp, or etc.) doesn't affect the results.
`locus.label` | vector of labels for the set of loci
`weight` | weights for observations (rows of geno matrix).
`mh.threshold` | threshold for the Mantel-Haenszel statistic that evaluates whether a locus contributes additional information of haplotype association to disease, conditional on current haplotypes. The default is 3.84, which is the 95th percentile of the chi-square distribution with 1 degree of freedom.
`r2.threshold` | threshold for a locus to be skipped. When scanning locus k, loci with correlations r-squared (the square of the Pearson's correlation) greater than r2.threshold with locus k will be ignored, so that the haplotype growing process continues for markers that are further away from locus k.
`haplo.freq.min` | the minimum haplotype frequency for a haplotype to be included in the association tests. The haplotype frequency is based on the EM algorithm that estimates haplotype frequencies independent of trait.
`miss.val` | vector of values that represent missing alleles.
`sim.control` | A list of control parameters to determine how simulations are performed for permutation p-values, similar to the strategy in haplo.score. The list is created by the function score.sim.control and the default values of this function can be changed as desired. Permutations are performed until a p.threshold accuracy rate is met for the three region-based p-values calculated in seqhap. See score.sim.control for details.
`control` | A list of parameters that control the EM algorithm for estimating haplotype frequencies when phase is unknown. The list is created by the function haplo.em.control - see this function for more details.
`x` | a seqhap object to print
`digits` | Number of significant digits to print for numeric values
`...` | Additional parameters for the print method

### Details

No further details

### Value

list with components:

`converge` | indicator of convergence of the EM algorithm (see haplo.em); 1 = converge, 0=failed
`locus.label` | vector of labels for loci
`pos` | chromosome positions for loci, same as input.
`n.sim` | number of permutations performed for emperical p-values
`inlist` | matrix that shows which loci are combined for association analysis in the sequential scan. The non-zero values of the kth row of inlist are the indices of the loci combined when scanning locus k.
`chi.stat` | chi-square statistics of single-locus analysis.
`chi.p.point` | permuted pointwise p-values of single-locus analysis.
`chi.p.region` | permuted regional p-value of single-locus analysis.
`hap.stat` | chi-square statistics of sequential haplotype analysis.
`hap.df` | degrees of freedom of sequential haplotype analysis.
`hap.p.point` | permuted pointwise p-values of sequential haplotype analysis.
`hap.p.region` | permuted region p-value of sequential haplotype analysis.
`sum.stat` | chi-square statistics of sequential summary analysis.
`sum.df` | degrees of freedom of sequential summary analysis.
`sum.p.point` | permuted pointwise p-values of sequential summary analysis.
`sum.p.region` | permuted regional p-value of sequential summary analysis.

### References

Yu Z, Schaid DJ. (2007) Sequential haplotype scan methods for association analysis. Genet Epidemiol, in print.

### See Also

`haplo.em`, `print.seqhap`, `plot.seqhap`, `score.sim.control`

### Examples

    # load example data with response and genotypes.
    data(seqhap.dat)
    mydata.y <- seqhap.dat[,1]
    mydata.x <- seqhap.dat[,-1]
    # load positions
    data(seqhap.pos)
    pos <- seqhap.pos$pos
    # run seqhap with default settings
    ## Not run:
      # this example takes 5-10 seconds to run
      myobj <- seqhap(y=mydata.y, geno=mydata.x, pos=pos)
      print.seqhap(myobj)

    ## End(Not run)

[Package haplo.stats version 1.7.9 Index]