single.haplotype.test: single haplotype test

Description

Association test based on haplotypes. Haplotypes are estimated by EM algorithm.

Usage

single.haplotype.test(snps, trait, famid, patid, fid, mid,  adj.var = NULL, type = c("gaussian", "binomial", "families"), prt = TRUE, lim = 0.05, min.count = 10,  alpha = 0.05, sort = FALSE)

Arguments

snps

(n.m)-Matrix; n=No. of individuals; m=no. of SNPs; Rohde-Code

trait

numeric; Outcome, phenotype

famid

vector; Identifier for every family; only need in case of type=families

patid

vector; Identifier for every individuals; only need in case of type=families

fid

vector; Identifier for father (0=unkown); only need in case of type=families

mid

vector; Identifier for mother (0=unkown); only need in case of type=families

adj.var

(n,m)-Matrix; n=No. of individuals; m=no. of covariates; variables for adjustment; in case of type=families not available.

type

type of depending variable

lim

numeric; threshold for pooling of haplotypes and declare as rare.

min.count

Minimal count for using pooled rare haplotypes in the analysis.

prt

A logical value (TRUE or FALSE). If TRUE, an overview is printed.

alpha

In case of type=binomial the (1-alpha/2)-confidence intervals are computed.

sort

A logical value (TRUE or FALSE). Only usable with family data. If TRUE, families are sorted by famid and generation which is a condition of wTDT.

Value

hap: Haplotypes
freq: Estimated haplotype frequencies
global.test: Result of global test statistic.
haplotype.i: Result of haplotype specific tests

Details

Haplotypes are infered by EM algorithm (Excoffier and Slatkin 1995). For normal distributed phenotypes from independent individuals we prefer an F test and for case control data we prefer the likelihood ratio test (logistic regression) in comparison of full model with genetic and non-genetic factors to a reduced model, which includes only non-genetic variables. In the case of no specified non-genetic variable only the intercept is used. If one of these tests are significance we assume a genetic effect. In case of family data the weigthed TDT statistic is used.

References

Excoffier L, Slatkin M. Mol Biol Evol. 1995 Sep;12(5):921-7. Rohde K, Fuerst R. Hum Hered. 2003;56(1-3):41-7. Rohde K, Fuerst R. Hum Mutat. 2001 Apr;17(4):289-95.

Knueppel S, Esparza-Gordillo J, Marenholz I, Holzhuetter HG,

Bauerfeind A, Ruether A, Weidinger S, Lee Y-A, Rohde K.

Multi-locus stepwise regression: a haplotype-based algorithm

for finding genetic associations applied to atopic dermatitis.