CCAFE

Case Control Allele Frequency (AF) Estimation R Package

This repository contains the source code for the CaseControlAF R package which can be used to reconstruct the allele frequency (AF) for cases and controls separately given commonly available summary statistics.

The package contains two functions:

1. CaseControl_AF
2. CaseControl_SE

See full documentation, vignettes, and examples here: (https://wolffha.github.io/CCAFE_documentation/)

Download the package

To install this package using BioConductor (Not yet available):

if (!require("BiocManager", quietly = TRUE))
    install.packages("BiocManager")

BiocManager::install("CCAFE")

To download this package using devtools in R:

require(devtools)
devtools::install_github("https://github.com/wolffha/CCAFE/")

CaseControl_AF

Use this function when you have the following statistics (for each variant)

• Number of cases
• Number of controls
• Odds Ratio (OR) or beta coefficient
• AF (allele frequency) for the total sample (cases and controls combined)

Usage

data: a dataframe with a row for each variant and columns for OR and total AF

N_case: an integer for the number of case samples

N_control: an integer for the number of control samples

OR_colname: a string containing the exact column name in 'data' with the OR

AF_total_colname: a string containing the exact column name in 'data' with the total AF

Returns a dataframe with two columns: AF_case and AF_control. The number of rows is equal to the number of variants.

CaseControl_SE

Use this function when you have the following statistics (for each variant)

• Number of cases
• Number of controls
• Odds Ratio (OR) or beta coefficient
• SE of the log(OR) for each variant

Code adapted from ReACt GroupFreq function available here: (https://github.com/Paschou-Lab/ReAct/blob/main/GrpPRS_src/CountConstruct.c)

Usage

data: a dataframe where each row is a variant and columns for the OR, SE, chromosome, and position

N_case: an integer for the number of case samples

N_control: an integer for the number of control samples

OR_colname: a string containing the exact column name in data with the odds ratios

SE_colname: a string containing the exact column name in data with the standard errors

position_colname: a string containing the exact column name in data with the positions of the variants

chromosome_colname: a string containing the exact column name in data with the chromosome of the variants. Note, sex chromosomes can be either characters ('X', 'x', 'Y', 'y') or numeric where X=23 and Y=24

sex_chromosomes: boolean, TRUE if variants from sex chromosome(s) are included in the dataset

do_correction: boolean, TRUE if data is provided to correct the estimates using proxy MAFs

remove_sex_chromosomes: boolean, TRUE if variants on sex chromosomes should be removed. This is only necessary if sex_chromosomes == TRUE and the number of XX/XY individuals per case and control sample is NOT known

CaseControl_SE has the following optional inputs:

If sex_chromosomes == TRUE and remove_sex_chromosomes == FALSE, then the following inputs are required:

N_XX_case: the number of XX chromosome case individuals

N_XX_control: the number of XX chromosome control individuals

N_XY_case: the number of XY chromosome case individuals

N_XY_control: the number of XY chromosome control individuals

If do_correction == TRUE, then data must be provided that includes harmonized data with proxy MAFs

correction_data: a dataframe with the following EXACT column names: CHR, POS, proxy_MAF, containing data for variants harmonized between the observed and proxy datasets

Returns the data dataframe with three additional columns with names: MAF_case, MAF_control and MAF_total containing the estimated minor allele frequency in the cases, controls, and total sample. The number of rows is equal to the number of variants. If proxyMAFs_colname is not NA, will include three additional columns containing the adjusted estimated MAFs (MAF_case_adj, MAF_control_adj, MAF_total_adj)

NOTE: This method assumes we are estimating the minor allele frequency (MAF)

Examples and documentation

See full documentation, vignettes, and examples here: (https://wolffha.github.io/CCAFE_documentation/)