Sliding_Window: Genetic region analysis of sliding windows using STAAR...

In xihaoli/STAARpipeline: STAARpipeline for Analyzing Whole-Genome/Whole-Exome Sequencing Data

Genetic region analysis of sliding windows using STAAR procedure

Description

The Sliding_Window function takes in chromosome, starting location, ending location, sliding window length, the object of opened annotated GDS file, and the object from fitting the null model to analyze the association between a quantitative/dichotomous phenotype (including imbalanced case-control design) and variants in a genetic region by using STAAR procedure. For each sliding window, 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. For imbalance case-control setting, the results correspond to the STAAR-B p-value, which is a p-value from an omnibus test that aggregated Burden(1,25) and Burden(1,1) together with p-values of each test weighted by each annotation using Cauchy method. For multiple phenotype analysis (obj_nullmodel$n.pheno > 1), the results correspond to multi-trait association p-values (e.g. MultiSTAAR-O) by leveraging the correlation structure between multiple phenotypes.

Usage

Sliding_Window(
  chr,
  start_loc,
  end_loc,
  sliding_window_length = 2000,
  type = c("single", "multiple"),
  genofile,
  obj_nullmodel,
  rare_maf_cutoff = 0.01,
  rv_num_cutoff = 2,
  rv_num_cutoff_max = 1e+09,
  rv_num_cutoff_max_prefilter = 1e+09,
  QC_label = "annotation/filter",
  variant_type = c("SNV", "Indel", "variant"),
  geno_missing_imputation = c("mean", "minor"),
  Annotation_dir = "annotation/info/FunctionalAnnotation",
  Annotation_name_catalog,
  Use_annotation_weights = c(TRUE, FALSE),
  Annotation_name = NULL,
  SPA_p_filter = TRUE,
  p_filter_cutoff = 0.05,
  silent = FALSE
)

Arguments

chr	chromosome.
start_loc	starting location (position) of the genetic region to be analyzed using STAAR procedure.
end_loc	ending location (position) of the genetic region to be analyzed using STAAR procedure.
sliding_window_length	the (fixed) length of the sliding window to be analyzed using STAAR procedure.
type	the type of sliding window to be analyzed using STAAR procedure. Choices include single, multiple (default = single).
genofile	an object of opened annotated GDS (aGDS) file.
obj_nullmodel	an object from fitting the null model, which is either the output from fit_nullmodel function, or the output from fitNullModel function in the GENESIS package and transformed using the genesis2staar_nullmodel function.
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).
rv_num_cutoff_max	the cutoff of maximum number of variants of analyzing a given variant-set (default = 1e+09).
rv_num_cutoff_max_prefilter	the cutoff of maximum number of variants before extracting the genotype matrix (default = 1e+09).
QC_label	channel name of the QC label in the GDS/aGDS file (default = "annotation/filter").
variant_type	type of variant included in the analysis. Choices include "SNV", "Indel", or "variant" (default = "SNV").
geno_missing_imputation	method of handling missing genotypes. Either "mean" or "minor" (default = "mean").
Annotation_dir	channel name of the annotations in the aGDS file (default = "annotation/info/FunctionalAnnotation").
Annotation_name_catalog	a data frame containing the name and the corresponding channel name in the aGDS file.
Use_annotation_weights	use annotations as weights or not (default = TRUE).
Annotation_name	a vector of annotation names used in STAAR (default = NULL).
SPA_p_filter	logical: are only the variants with a normal approximation based p-value smaller than a pre-specified threshold use the SPA method to recalculate the p-value, only used for imbalanced case-control setting (default = TRUE).
p_filter_cutoff	threshold for the p-value recalculation using the SPA method, only used for imbalanced case-control setting (default = 0.05).
silent	logical: should the report of error messages be suppressed (default = FALSE).

Value

A data frame containing the STAAR p-values (including STAAR-O or STAAR-B in imbalanced case-control setting) corresponding to each sliding window in the given genetic region.

References

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)

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)

xihaoli/STAARpipeline documentation built on Feb. 9, 2025, 12:39 a.m.