SKAT_CommonRare: SKAT for the combined effect of rare and common variants
In ttimbers/SKAT: SNP-Set (Sequence) Kernel Association Test

Description Usage Arguments Details Value Author(s) References Examples

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

	SKAT_CommonRare(Z, obj, weights.beta.rare=c(1,25), weights.beta.common=c(0.5,0.5)
	, 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, ...)

	SKAT_CommonRare.SSD.OneSet_SetIndex(SSD.INFO, SetIndex, obj, ... )

	SKAT_CommonRare.SSD.All(SSD.INFO, obj, ...)

`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)).
`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 collapsing test, respectively
`r.corr.common`	the ρ parameter for common variants (default= 0). ρ =0 and 1 indicate SKAT and collapsing 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
`...`	furthuer arguments to be passed to “SKAT_CommonRare”

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

`p.value`	the p-value.
`p.value.resampling`	the p-value from resampled outcome. 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.
`results`	(SKAT_CommonRare.SSD.All only) the dataframe that contains SetID, p-values (P.value), the number of markers in the SNP sets (N.Marker.All), the number of markers to test for an association after excluding non-polymorphic or high missing rates markers (N.Marker.Test), and the number of rare (N.Marker.Rare) and common (N.Marker.Common) variants used for association tests.
`P.value.Resampling`	(SKAT_CommonRare.SSD.All only) the matrix that contains p-values of resampled phenotypes.

Seunggeun Lee

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.

data(SKAT.example)
attach(SKAT.example)



# continuous trait
obj<-SKAT_Null_Model(y.c ~ X, out_type="C")
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")

# 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