CollapsABEL: CollapsABEL: an R library for detecting compound heterozygote alleles in genome-wide association or sequencing studies
Description
Compound Heterozygosity (CH) in classical genetics is the presen-ce of two
different recessive mutations at a particular gene locus, one on each chromosome
. The presence of CH has been found for nearly all
autosomal recessive disorders as well as other phenotypes such as red hair
color. A relaxed form of CH, i.e., in which the genetic variants are not
necessarily coding, rare, and deleterious, is likely involved in a wide range of
human polygenic traits and referred to as generalized CH (GCH). Howev-er,
individually analyzing a large number of DNA sequence vari-ants, as being the
routine in genome-wide association studies (GWAS), has limited power to detect
genetic associations caused by GCH, which may be partially responsible for the
currently still "missing heritability".
Existing tools specifically designed for detecting GCH alleles are scarce, in
particular for the analysis of densely imputed Single Nucleotide Polymorphism
(SNP) array data or whole genome se-quencing data. Previously, we developed a
collapsed double heter-ozygosity (CDH) test for detecting the association
between CH genotypes and binary traits by applying a chi-squared statistic to
pseudo-genotypes collapsed from a pair of SNPs, which was
implemented as a function in the GenABEL R package .
Here, we implement a generalized CDH (GCDH) method to overcome previous
limitations and allow (1) fast analysis of densely imputed SNP data or whole
genome se-quencing data; (2) flexible analysis of binary and quantitative traits
with covariates; (3) empirical power estimation and type-I error control; and
(4) easy interface with graphical utilities
Arguments
phe_file
character. Phenotype file.
Value
FALSE when the file is invalid, or a data.frame when it is.