Description Usage Arguments Details Value Author(s) References Examples
Fit Cox proportional hazards regression model with shared frailty (random
effect) in each pedigree for single SNP analysis that tests associations between
a survival phenotype and each genotyped SNP on a chromosome in a genotype file
and for gene-based tests in family data. The association test is carried out by
coxph.EC
function. Likelihood ratio test (LRT) result is reported. In each
test, the coxph
function from package survival
is used.
1 2 3 4 |
genfile |
a character string naming the genotype file for reading |
phenfile |
a character string naming the phenotype file for reading |
pedfile |
a character string naming the pedigree file for reading |
phen |
a character string for the phenotype name of a survival trait of
interest in |
covars |
a character vector for covariates in |
sep.ped |
the field separator character for pedigree file |
sep.phe |
the field separator character for phenotype file |
sep.gen |
the field separator character for genotype file |
time |
the character string of variable named for survival time |
mafRange |
range of MAF to include SNPs for gene-based burden tests, default is c(0,0.05) |
chr |
chromosome number that can be 1,2,...,22, and 'X' |
snpinfoRdata |
a character string naming the RData containing SNP info to be loaded, this should at least include 'Name' (for SNP name), 'Chr', and aggregateBy (default='SKATgene') columns |
aggregateBy |
the column of SNP info on which single SNPs are to be aggregated for burden tests, default is 'SKATgene' |
maf.file |
a character string naming the comma delimited file containing 'Name' for SNP name and 'maf' for MAF |
snp.cor |
a character string naming the RData containing lists of SNP correlation matrix within each 'SKATgene' |
ssq.beta.wts |
a vector of parameters of beta weights used in proposed sum of squares test, default=c(1,25) as in SKAT |
singleSNP.outfile |
a logical value, TRUE indicating single SNP analysis has been done
and result files are available for computing SSQ using a different |
The coxph.ped
function reads in and merges phenotype, genotype, and pedigree files to
perform single SNP analysis, two burden tests (weight=1 for Li & Leal 2008; weight=1/(MAF)/(1-MAF)
for Madsen & Browning 2009), and one sum of squares (SSQ) test (Wei 2009) using Cox proportional
hazards regression model with shared frailty (random effect) in each family as implemented
in coxph
function in survival
R package and to output an RData that is computed
based on single SNP results and that is compatible with seqMeta
R package for conducting
meta-analysis. For burden tests and SSQ test, SNPs genotypes/results are aggregated by
aggregateBy
(default = "SKATgene") using SNPs selected according to user specified
mafRange
within each gene (by default). genfile
contains unique individual numerical
id and genotype data on a chromosome, with the column names being "id" and SNP names. For each SNP,
the genotype data should be coded as 0, 1, 2 indicating the numbers of the coded alleles. The SNP
name in genotype file should not have any dash, '-' and other special characters(dots and
underscores are OK). phenfile
contains unique individual id, phenotype and covariates data,
with the column names being "id" and phenotype and covaraite names. pedfile
contains
pedigree informaion, with the column names being "famid","id","fa","mo","sex". LRT is used
in all genetic association tests.
No value is returned. Instead, tab delimited result files and an RData are generated. A single
SNP result file, named with phen
and singleSNP, contains columns: gene
, Name
,
maf
, ntotal
, nmiss
, maf_ntotal
, beta
, se
, Z
,
remark
, p
(p-value from LRT), MAC
, n0
, n1
, and n2
.
A burden test result file, named with phen
and T/MB for Li & Leal 2008/Madsen & Browning
2009 respectively, contains columns: gene
, beta
, se
, Z
,
cmafTotal
, cmafUsed
, nsnpsTotal
, nsnpsUsed
, nmiss
,
remark
, and p
. A SSQ test result file, named with phen
and SSQ, contains
columns: gene
, SSQ
, cmafTotal
, cmafUsed
, nsnpsTotal
,
nsnpsUsed
, nmiss
, df
, and p
. A generated RData that is a list that
contains scores
, cov
, n
, maf
and sey
for each gene with
gene names being the names of the list. Note maf
in RData is MAF based on ntotal.
gene |
gene name |
Name |
SNP name |
maf |
minor allele frequency based on genotyped sample |
ntotal |
number of individuals with genotype, phenotype and covariates |
nmiss |
number of individuals with missing genotype among |
maf_ntotal |
minor allele frequency based on |
beta |
regression coefficient of single SNP test or burden test |
se |
standard error of |
Z |
signed likelihood ratio statistic |
remark |
additional information of the analysis |
p |
p-value of single SNP test or burden test by LRT |
camfTotal |
sum of |
cmafUsed |
sum of |
nsnpsTotal |
total number of SNPs in a gene |
nsnpsUsed |
number of SNPs selected and used in burden tests and SSQ test |
SSQ |
sum of squares statistic |
df |
degrees of freedom of SSQ |
MAC |
minor allele count |
n0 |
the number of individuals with 0 copy of coded alleles |
n1 |
the number of individuals with 1 copy of coded alleles |
n2 |
the number of individuals with 2 copies of coded alleles |
scores |
|
cov |
diag(1/se)*LD matrix*diag(1/se) in output RData |
n |
maximum |
sey |
1 in output RData |
Ming-Huei Chen <mhchen@bu.edu> and Qiong Yang <qyang@bu.edu>
Therneau T (2014). A Package for Survival Analysis in S. R package version 2.37-7, http://CRAN.R-project.org/package=survival.
Terry M. Therneau and Patricia M. Grambsch (2000). Modeling Survival Data: Extending the Cox Model. Springer, New York. ISBN 0-387-98784-3.
Li, B. and Leal, S. M (2008). Methods for Detecting Associations with Rare Variants for Common Diseases: Application to Analysis of Sequence Data. Am J Hum Genet, 83(3), 311-321.
Madsen, B. E. and Browning, S. R (2009). A Groupwise Association Test for Rare Mutations Using a Weighted Sum Statistic. PLoS Genet, 5(2) e1000384.
Wei P (2009). Asymptotic Tests of Association with Multiple SNPs in Linkage Disequilibrium. Genet Epidemiol, 33(6), 497-507.
1 2 3 4 5 6 7 8 | ## Not run:
coxph.ped(genfile="EC_chr1.txt",phenfile="trait1.csv",pedfile="ped.csv",
phen="trait1",covars=NULL,sep.ped=",",sep.phe=",",sep.gen=" ",
mafRange=c(0,0.01),chr=1,snpinfoRdata="SNPinfo_EC.RData",
aggregateBy="SKATgene",time="survival_time",maf.file="EC_MAF.csv",
snp.cor="EC_SNPcor.RData")
## End(Not run)
|
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