Introduction to CoPheScan

In cophescan: Adaptation of the Coloc Method for PheWAS

knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>",
  fig.path = "Intro-"
)

library(cophescan)

CoPheScan

The cophescan package implements Coloc adapted Phenome-wide Scan (CoPheScan), a Bayesian method to perform Phenome-wide association studies (PheWAS) that identifies causal associations between genetic variants and phenotypes while simultaneously accounting for confounding due to linkage disequilibrium.

Given a query variant and genomic region with Q SNPs for a query trait, cophescan discriminates between 3 hypotheses:

$H_n$ : No association with the query trait (1 configuration)

$H_a$ : Association of a variant other than the query variant with the query trait (Q-1 configurations)

$H_c$ : Association of the query variant with the query trait (1 configuration)

with $p_n$, $p_a$ and $p_c$ being their corresponding priors.

CoPheScan approaches

cophescan can be run in different ways depending on the size and type of dataset.

First, choosing the method for Bayes factor computation:

| | Single causal variant | Multiple causal variants | Requires LD matrix | |-------|-----------------------|--------------------------|--------------------| | ABF | ✔ | x | No | | SuSIE | ✔ | ✔ | Yes | | | | | |

Whenever, LD matrices are available (preferably in-sample LD), `cophe.susie` is the recommended method as it accounts for multiple causal variants in the tested region.

Next, depending upon the size of the dataset we choose the method to specify priors :

| | Dataset | Inclusion of covariates | |---------------------|---------|-------------------------| | Fixed priors | Small | - | | Hierarchical priors | Large | ✔ | | | | |

The different combinations that can be run are:

ABF/Fixed priors: cophe.single

SuSIE BF/Fixed priors: cophe.susie

ABF/Hierarchical priors: cophe.single.lbf + run_metrop_priors

SuSIE BF/Hierarchical priors: cophe.susie.lbf + run_metrop_priors

Further reading

1. Description of the CoPheScan method:

   CoPheScan: phenome-wide association studies accounting for linkage disequilibrium

2. coloc: Giambartolomei et al (2013)

3. coloc with SuSIE: Wallace et al (2021), github

4. ABF: Wakefield (2008)

5. SuSIE: Wang et al (2020), github

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cophescan documentation built on June 22, 2024, 9:15 a.m.