mtAssociation: mtAssociation function

In mtDNA-BU/ANNOmtDNA: Annotation of mtDNA sequence variations

mtAssociation function

Description

Association analysis of heteroplasmies with disease traits by four common methods of burden test, SKAT, SKAT-O and ACAT-O. ACAT-O is used to combine results of burden test and SKAT.

Usage

mtAssociation(
  aaf,
  coverage,
  coverage.qc = 250,
  family,
  pheno,
  trait,
  covars,
  G_coding = "heter",
  rho_skatO = c(0, 1),
  heter_scale = F,
  region = c(1:16569),
  thre_lower = 0.03,
  thre_upper = 0.97,
  maf_max = 0.01,
  kins = NULL
)

Arguments

aaf	a numeric matrix (16569 x N) provided by the user. Rows correspond to loci and columns correspond to subjects. It contains subject ID as the column names, and the AAFs of all 16569 mtDNA loci for each subject. It is generated from mtAAF function.
coverage	a numeric matrix (16569 x N) provided by the user. Rows correspond to loci and columns correspond to subjects. This matrix contains the reads coverage of the 16569 mtDNA loci for each subject. The matrix must contain the subject ID as the column names.
coverage.qc	a number(default is 250) of threshold for the coverage. If the coverage<coverage.qc, the allele call at that locus of the subject will not be used.
family	a character string to specify data type of outcome: "gaussian" for continuous data and "binomial" for binary data.
pheno	a data frame containing data of covariates and outcome. Rows are subjects and columns are variables. It must have the same sample size as the aaf matrix. It must contain the subject ID as the row names.
trait	a character string of outcome name to be analyzed.
covars	a character vector indicating the names of covariates.
G_coding	Coding definition of heteroplasmy. "heter" for coding definition 1, and "heter2" for coding definition 2. See details.
rho_skatO	A sequence of values that specify combinations of SKAT and a burden test to be considered in SKAT-O (default is c(0,1)).
heter_scale	logical(default is False). A user can specify to standardize the genetic dosage of heteroplasmies of each variant.
region	a numeric vector to specify the gene region to be analyzed (default is c(1:16569)).
thre_lower	a number (default is 0.03) of lower bound of the threshold defining heteroplasmic mutations
thre_upper	a number (default is 0.97) of upper bound of the threshold defining heteroplasmic mutations
maf_max	upper bound of frequency of heteroplasmies at population level to be included
kins	Kinship matrix for related subjects. Only support for continuous outcomes currently.

Details

By coding definition 1 (G_coding="heter"), the genetic dosage of heteroplasmy is 1 if the corresponding alternative allele fraction (aaf) satisfies thre_lower≤aaf≤thre_upper, and 0 otherwise. By coding definition 2 (G_coding="heter2"), the genetic dosage of heteroplasmy is the aaf itself if the corresponding alternative allele fraction (aaf) satisfies thre_lower≤aaf≤thre_upper, and 0 otherwise.

Value

A data frame containing the results of association analysis of heteroplasmies by the four methods.

Examples

## Not run: 
## Read input data

aaf_file <- "aaf.csv"
coverage_file <- "coverage.csv"
pheno_file <- "pheno.csv"

aaf <- as.matrix(read.csv(file = aaf_file, sep = ","))
coverage <- as.matrix(read.csv(file = coverage_file, sep = ","))
pheno <- read.csv(file = pheno_file, sep = ",")

mtAssociation(aaf=aaf, coverage=coverage, family="gaussian", pheno=pheno,
trait="BMI", covars=c("AGE", "SEX"))


## End(Not run)

mtDNA-BU/ANNOmtDNA documentation built on Aug. 11, 2022, 1:46 p.m.