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Updated: Jun 23, 2026

Large-Scale Multi-Omics Genome-Wide Association Studies (Mo-GWAS): Guidelines for Sample Preparation and Normalization
Published on: July 27, 2021
Validating, augmenting and refining genome-wide association signals
John P A Ioannidis1, Gilles Thomas, Mark J Daly
1Department of Hygiene and Epidemiology, University of Ioannina School of Medicine and Biomedical Research Institute, Foundation for Research and Technology - Hellas, Ioannina 45110, Greece. jioannid@cc.uoi.gr
Abstract:
Studies using genome-wide platforms have yielded an unprecedented number of promising signals of association between genomic variants and human traits. This Review addresses the steps required to validate, augment and refine such signals to identify underlying causal variants for well-defined phenotypes. These steps include: large-scale exact replication across both similar and diverse populations; fine mapping and resequencing; determination of the most informative markers and multiple independent informative loci; incorporation of functional information; and improved phenotype mapping of the implicated genetic effects. Even in cases for which replication proves that an effect exists, confident localization of the causal variant often remains elusive.
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