SKAT_CommonRare: SKAT for the combined effect of common and rare variants

In SKAT: SNP-Set (Sequence) Kernel Association Test

SKAT for the combined effect of common and rare variants

Description

Sequence Kernel association test for the combined effect of common and rare variants.

Usage

	SKAT_CommonRare(Z, obj, weights.beta.rare=c(1,25)
	, weights.beta.common=c(0.5,0.5), weights=NULL
	, method="C", r.corr.rare=0, r.corr.common=0, CommonRare_Cutoff=NULL
	, test.type="Joint", is_dosage=FALSE, missing_cutoff=0.15
	, estimate_MAF=1, SetID1=NULL)


	SKAT_CommonRare.SSD.OneSet(SSD.INFO
	, SetID, obj, ..., obj.SNPWeight=NULL)

	SKAT_CommonRare.SSD.OneSet_SetIndex(SSD.INFO
	, SetIndex, obj, ..., obj.SNPWeight=NULL )


	
 

Arguments

Z	a numeric genotype matrix with each row as a different individual and each column as a separate gene/snp. Each genotype should be coded as 0, 1, 2, and 9 (or NA) for AA, Aa, aa, and missing, where A is a major allele and a is a minor allele. Missing genotypes will be imputed by the simple Hardy-Weinberg equilibrium (HWE) based imputation.
obj	an output object of the SKAT_Null_Model function.
weights.beta.rare	a numeric vector of parameters of beta weights for rare variants (default=c(1,25)).
weights.beta.common	a numeric vector of parameters of beta weights for common variants (default=c(0.5,0.5)).
weights	a numeric vector of weights for both common and rare variants. When it is NULL, the beta weight with the “weights.beta.rare” and “weights.beta.common” parameter are used. When method ="C", the coefficient to combine common and rare variants test statistics will be calculated after applying the weights to variants.
method	a method to combine common and rare variant effects (default="C"). "C" represents the combined sum test, and "A" represents the adaptive sum test. "AR" represents a different type of adaptive test in which common variants are projected over rare variants.
r.corr.rare	the ρ parameter for rare variants (default= 0). ρ =0 and 1 indicate SKAT and Burden test, respectively
r.corr.common	the ρ parameter for common variants (default= 0). ρ =0 and 1 indicate SKAT and Burden test, respectively
CommonRare_Cutoff	MAF cutoff for common vs rare variants (default=NULL). It should be a numeric value between 0 and 0.5, or NULL. When it is NULL, 1/ √{2 SampleSize } will be used.
test.type	a string to indicate test type (default="Joint"). "Joint" indicates the joint test of the combined effects of common and rare variants. "Rare.Only" and "Common.Only" will conduct test only with rare and common variants, respectively.
is_dosage	see SKAT
missing_cutoff	see SKAT
estimate_MAF	see SKAT
SetID1	internal use only
SSD.INFO	an SSD_INFO object returned from Open_SSD.
SetID	a character value of Set ID. You can find a set ID of each set from SetInfo object of SSD.INFO
SetIndex	a numeric value of Set index. You can find a set index of each set from SetInfo object of SSD.INFO
obj.SNPWeight	output object from Read_SNP_WeightFile (default=NULL). If NULL, the beta weight with the “weights.beta” parameter will be used.
...	furthuer arguments to be passed to “SKAT_CommonRare”

Details

The small sample adjustment for binary traits is not implemented for "A" and "AR".

Value

p.value	p-value.
p.value.resampling	p-values from resampled phenotypes. You can get it when you use obj from SKAT_Null_Model function with resampling. See the SKAT_Null_Model.
n.rare	the number of rare variants used for the test
n.common	the number of common variants used for the test
Cutoff	the MAF cut-off to divide common and rare variants
Q	the test statistic of SKAT. It has NA when method="A" or "AR".
param	estimated parameters of each method.
param$Is_Converged	an indicator of the convergence. 1 indicates the method is converged, and 0 indicates the method is not converged. When 0 (not converged), "liu.mod" method is used to compute p-value.
param$n.marker	a number of SNPs in the genotype matrix
param$n.marker.test	a number of SNPs used for the test. It can be different from param$n.marker when some markers are monomorphic or have higher missing rates than the missing_cutoff.
test.snp.mac	a vector of minor allele count (MAC) of the snps tested. The name is SNP-ID.

Author(s)

Seunggeun Lee

References

Ionita-Laza, I.*, Lee, S.*, Makarov, V., Buxbaum, J. Lin, X. (2013). Sequence kernel association tests for the combined effect of rare and common variants. American Journal of Human Genetics, 92, 841-853. * contributed equally.

Examples

data(SKAT.example)
Z<-SKAT.example$Z


# continuous trait
obj<-SKAT_Null_Model(y.c ~ X, out_type="C", data=SKAT.example)
SKAT_CommonRare(Z, obj)$p.value
SKAT_CommonRare(Z, obj, method="A")$p.value
SKAT_CommonRare(Z, obj, method="AR")$p.value


# dichotomous trait 
obj<-SKAT_Null_Model(y.b ~ X, out_type="D", data=SKAT.example)

# Combined sum test in the manuscript (SKAT-C and Burden-C)
SKAT_CommonRare(Z, obj)$p.value
SKAT_CommonRare(Z, obj, r.corr.rare=1, r.corr.common=1 )$p.value


# Test only with common variant
SKAT_CommonRare(Z, obj, test.type="Common.Only")$p.value

# Test only with rare variant
SKAT_CommonRare(Z, obj, test.type="Rare.Only")$p.value


# Use CommonRare_Cutoff=0.01 instead of CommonRare_Cutoff = NULL
SKAT_CommonRare(Z, obj, CommonRare_Cutoff=0.01)$p.value

# Use custom weights; the first 10 variants have higher weights 
weights<-rep(1,67); weights[1:10]<-2
SKAT_CommonRare(Z, obj, weights=weights)$p.value

SKAT documentation built on Jan. 15, 2023, 5:10 p.m.