Overview of retrospective saddlepoint approximation (SPA) methods in GWAS

The retrospective saddlepoint approximation (SPA) methods are mainly designed to conduct genome-wide association studies (GWAS) in terms of both single-variant and set-based analysis.

Genome-wide association studies

All retrospective-SPA-based GWAS approaches share the same analysis framework including the following two steps

  • Step 1: Fit a null model using trait, covariates, and GRM (if applied).
  • Step 2: Conduct single-variant or set-based tests to identify marker or marker-set (e.g. gene) significantly associated with the trait of interest.

Genome-wide gene-environment interaction (GxE) studies

All retrospective-SPA-based GxE approaches share the same analysis framework including the following two steps:

  • Step 1: Fit a genotype-independent (covariates-only) model using trait, covariates, and GRM (if applied).
  • Step 2: Conduct single-variant or set-based tests to identify marker or marker-set (e.g. gene) significantly associated with the trait of interest.

Timeline of the Retrospective SPA Project

March 2021

  • Event: The idea of a retrospective saddlepoint approximation (SPA) was conceived.

October 2021

  • Event: The SPAmix algorithm was successfully designed.

October 2021 - February 2022

  • Event: Work on the SPAGxE algorithm was initiated.

May 2022

  • Event: The master’s thesis (DOI:10.27272/d.cnki.gshdu.2022.002946), which initially introduced the concept of retrospective SPA, was completed.

RetroSPA_timeline