# Divide and conquer approach for genome-wide association studies

## TL;DR

This paper introduces a faster and more efficient method for genome-wide association studies by splitting data into smaller parts and combining results.

## Contribution

A novel divide-and-conquer GWAS pipeline that reduces computational costs while maintaining accuracy and handling population structure.

## Key findings

- The pipeline achieves same discovery levels as standard GWAS with reduced computational costs.
- Effectively handles related individuals and controls inflated effect sizes in real datasets.
- Supports incremental analysis as new samples are added and improves reproducibility.

## Abstract

Genome-wide association studies (GWAS) are computationally intensive, requiring significant time and resources with computational complexity scaling at least linearly with sample size. Here, we present an accurate and resource-efficient pipeline for GWAS that mitigates the impact of sample size on computational demands. Our approach involves (1) randomly partitioning the cohort into equally sized sub-cohorts, (2) conducting independent GWAS within each sub-cohort, and (3) integrating the results using a novel meta-analysis technique that accounts for population structure and other confounders between sub-cohorts. Importantly, we demonstrate through simulations and real-data examples in humans that our approach effectively manages analyzing related individuals, a critical factor in real datasets, while controlling for inflated effect sizes, a phenomenon known as winner's curse. We show that our method achieves the same discovery levels as standard approaches but with significantly reduced computational costs. Additionally, it is well-suited for incremental GWAS as new samples are added over time. Our implementation within a bioinformatics workflow management system enhances reproducibility and scalability.