Genome-wide association studies (GWAS);
meta-analysis;
population structure;
winner's curse;
HERITABILITY;
TOOL;
METAANALYSIS;
RESOURCE;
D O I:
10.1093/genetics/iyaf019
中图分类号:
Q3 [遗传学];
学科分类号:
071007 ;
090102 ;
摘要:
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.
机构:
Univ Milan, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Mangiagalli & Regina Elena Fdn,Luigi Villa Fdn, IRCCS,Maggiore Hosp,Dept Med & Med Special, I-20122 Milan, ItalyUniv Milan, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Mangiagalli & Regina Elena Fdn,Luigi Villa Fdn, IRCCS,Maggiore Hosp,Dept Med & Med Special, I-20122 Milan, Italy