make_LDSR_annot (v: 2.4.6)

Collection of R functions to create annotations for analysis using stratified LDSC

NOTE: the R-functions only create the annotation-files, you still need to convert the annotation-files to LDscores (see: https://github.com/bulik/ldsc/wiki/LD-Score-Estimation-Tutorial )

There are two ways to create a new annotation:

1. specifying a set of SNPs to include
2. collapse existing annotations

Requirements

The function requires the data.table-package to be installed in R

Getting started

Clone this repository and:

1. run script_get_reference_file.sh (optional)
2. source make.LDSR.annot.R in R

1. Creating a new annotation by specifying a set of SNPs

To create a new annotation, run the make.LDSR.annot()-function

This function requires the following 5 arguments:

• input=vector or data.frame (see below)
• out=output directory
• annot.name=name for the new annotation
• template.dir=directory containing existing annotation files (see below)
• input.type=c("rs","id","name","bp","pos")

Other accepted arguments:

• sep=separator for the chromosome-basepair positions
• add.windows=add window-annotations (see below)
• GeneCode=reference file (see below)
• ID.extension=does the gene IDs contain extensions?
• gene.shoulder=add shoulder around genes (see below)

input

The function can handle 5 types of input:

• a list of RSIDs (input.type='rs')
• a list of gene IDs (input.type='id')
• a list of gene names (input.type='name')
• a list of chromosome:basepair ranges (input.type='bp')
• a list of chromosome:basepair positions (input.type='pos')

For a list of CHR:BP ranges, the input must be a three-column data.frame with the following order:

• CHR
• START
• END

In all other cases the input should be either (1) a vector or (2) a single-column data.frame or matrix

NOTE: for a list of gene IDs/names, an additional file is required that indicates which basepair positions are spanned by the genes (see below). This file can be created by running script_get_reference_file.sh

template.dir

Use this argument to indicate where the templates are located. For example, template.dir="/home/user/my_annotations/foo" results in the function using foo.[1-22].annot.gz as templates for the new annotation.

add.windows

As indicated by Finucane et al (2015), it is sometimes proper to add additional so-called window-annotations next to your main annotation. The window annotation includes all SNPs that are part of the main annotation and every SNP that is within a specific BP-window from these SNPs. The argument accepts one of the following values:

• an integer
• a vector of integers
• T(RUE)=add 100 and 500bp windows (default)
• F(ALSE)=do not add windows

GeneCode

This argument is used to indicate which OBJECT is the reference file that indicates the span of each gene. This object should contain the following 4 columns with these names:

• GENE_ID/GENE_NAME
• CHROMOSOME
• START
• END

NOTE: the object may contain more columns than required (e.g. both GENE_NAME and GENE_ID) as long as the column names of the relevant columns match exactly with what is shown above

gene.shoulder

When using genes as input, it is often prudent to extend the genes with a certain range (see Finucane et al, 2018). gene.shoulder accepts a single integer as input.

Note: this is different from specifying windows: add.windows=100 will return a file with two annotations, the main annotation and a 100-BP window; whereas gene.shoulder=100 returns one annotation where the ranges as specified by GeneCode are extended with 100 BP on both sides of the gene.

NOTE: if both add.windows and gene.shoulder are specified, gene ranges will first be extended and windows will be made based on the extended ranges

2. collapse existing annotations

Use the collapse.annots()-function to combine multiple annotations into a single annotation. You can choose to do one of two things:

• intersection=new annotation will only include SNPs that are common to all annotations
• union=new annotation will contain all SNPs that is part of at least one annotation

NOTE: the function has only been tested with files that contain only one annotation. The function may not work propberly with files that contain windows and/or consists of multiple annotations (e.g. the "baseline"-annotations).

The function requires 4 arguments:

• annot.dir=directory containing the annotations to collapse
• out=output directory
• annot.name=name for the new annotation
• collapse.type= "intersection" or "union" (case-sensitive)

Optional argument:

• add.windows (see above)

annot.dir

The value supplied to this argument should be a (vector of) strings. For example: annot.dir=c("/home/user/my_annotations/foo","/home/user/my_annotations/bar") indicates that foo.[1-22].annot.gz and bar.[1-22].annot.gz will be included in the new annotation.

Alternatively, the value may be a directory, e.g. annot.dir="/home/user/my_annotations/" (note the trailing slash!), and all annotations inside the annotation will be collapsed into the new annotation.

Output

Both functions return:

• 22 files called <annot.name>.[1-22].annot.gz
• <annot.name>.log

make.LDSR.annot() further returns:

• <annot.name>.included: list of SNPs/genes that were included in the new annotation
• <annot.name>.excluded: list of SNPs/genes that were excluded from the new annotation (if applicable)