STAAR: STAAR procedure using omnibus test

In xihaoli/STAAR: STAAR Procedure for Dynamic Incorporation of Multiple Functional Annotations in Whole-Genome Sequencing Studies

STAAR procedure using omnibus test

Description

The STAAR function takes in genotype, the object from fitting the null model, and functional annotation data to analyze the association between a quantitative/dichotomous phenotype and a variant-set by using STAAR procedure. For each variant-set, the STAAR-O p-value is a p-value from an omnibus test that aggregated SKAT(1,25), SKAT(1,1), Burden(1,25), Burden(1,1), ACAT-V(1,25), and ACAT-V(1,1) together with p-values of each test weighted by each annotation using Cauchy method.

Usage

STAAR(
  genotype,
  obj_nullmodel,
  annotation_phred = NULL,
  rare_maf_cutoff = 0.01,
  rv_num_cutoff = 2
)

Arguments

genotype	an n*p genotype matrix (dosage matrix) of the target sequence, where n is the sample size and p is the number of genetic variants.
obj_nullmodel	an object from fitting the null model, which is the output from either fit_null_glm function for unrelated samples or fit_null_glmmkin function for related samples. Note that fit_null_glmmkin is a wrapper of the glmmkin function from the GMMAT package.
annotation_phred	a data frame or matrix of functional annotation data of dimension p*q (or a vector of a single annotation score with length p). Continuous scores should be given in PHRED score scale, where the PHRED score of j-th variant is defined to be -10*log10(rank(-score_j)/total) across the genome. (Binary) categorical scores should be taking values 0 or 1, where 1 is functional and 0 is non-functional. If not provided, STAAR will perform the SKAT(1,25), SKAT(1,1), Burden(1,25), Burden(1,1), ACAT-V(1,25), ACAT-V(1,1) and ACAT-O tests (default = NULL).
rare_maf_cutoff	the cutoff of maximum minor allele frequency in defining rare variants (default = 0.01).
rv_num_cutoff	the cutoff of minimum number of variants of analyzing a given variant-set (default = 2).

Value

A list with the following members:

num_variant: the number of variants with minor allele frequency > 0 and less than rare_maf_cutoff in the given variant-set that are used for performing the variant-set using STAAR.

cMAC: the cumulative minor allele count of variants with minor allele frequency > 0 and less than rare_maf_cutoff in the given variant-set.

RV_label: the boolean vector indicating whether each variant in the given variant-set has minor allele frequency > 0 and less than rare_maf_cutoff.

results_STAAR_O: the STAAR-O p-value that aggregated SKAT(1,25), SKAT(1,1), Burden(1,25), Burden(1,1), ACAT-V(1,25), and ACAT-V(1,1) together with p-values of each test weighted by each annotation using Cauchy method.

results_ACAT_O: the ACAT-O p-value that aggregated SKAT(1,25), SKAT(1,1), Burden(1,25), Burden(1,1), ACAT-V(1,25), and ACAT-V(1,1) using Cauchy method.

results_STAAR_S_1_25: a vector of STAAR-S(1,25) p-values, including SKAT(1,25) p-value weighted by MAF, the SKAT(1,25) p-values weighted by each annotation, and a STAAR-S(1,25) p-value by aggregating these p-values using Cauchy method.

results_STAAR_S_1_1: a vector of STAAR-S(1,1) p-values, including SKAT(1,1) p-value weighted by MAF, the SKAT(1,1) p-values weighted by each annotation, and a STAAR-S(1,1) p-value by aggregating these p-values using Cauchy method.

results_STAAR_B_1_25: a vector of STAAR-B(1,25) p-values, including Burden(1,25) p-value weighted by MAF, the Burden(1,25) p-values weighted by each annotation, and a STAAR-B(1,25) p-value by aggregating these p-values using Cauchy method.

results_STAAR_B_1_1: a vector of STAAR-B(1,1) p-values, including Burden(1,1) p-value weighted by MAF, the Burden(1,1) p-values weighted by each annotation, and a STAAR-B(1,1) p-value by aggregating these p-values using Cauchy method.

results_STAAR_A_1_25: a vector of STAAR-A(1,25) p-values, including ACAT-V(1,25) p-value weighted by MAF, the ACAT-V(1,25) p-values weighted by each annotation, and a STAAR-A(1,25) p-value by aggregating these p-values using Cauchy method.

results_STAAR_A_1_1: a vector of STAAR-A(1,1) p-values, including ACAT-V(1,1) p-value weighted by MAF, the ACAT-V(1,1) p-values weighted by each annotation, and a STAAR-A(1,1) p-value by aggregating these p-values using Cauchy method.

References

Li, X., Li, Z., et al. (2020). Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale. Nature Genetics, 52(9), 969-983. (pub)

Li, Z., Li, X., et al. (2022). A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies. Nature Methods, 19(12), 1599-1611. (pub)

Liu, Y., et al. (2019). Acat: A fast and powerful p value combination method for rare-variant analysis in sequencing studies. The American Journal of Human Genetics, 104(3), 410-421. (pub)

Li, Z., Li, X., et al. (2020). Dynamic scan procedure for detecting rare-variant association regions in whole-genome sequencing studies. The American Journal of Human Genetics, 104(5), 802-814. (pub)

xihaoli/STAAR documentation built on Jan. 27, 2024, 8:51 a.m.