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Updated: Dec 21, 2025

Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization
Published on: July 27, 2021
Population phenomena inflate genetic associations of complex social traits
Tim T Morris1,2, Neil M Davies1,2,3, Gibran Hemani1,2
1Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
Abstract:
Heritability, genetic correlation, and genetic associations estimated from samples of unrelated individuals are often perceived as confirmation that genotype causes the phenotype(s). However, these estimates can arise from indirect mechanisms due to population phenomena including population stratification, dynastic effects, and assortative mating. We introduce these, describe how they can bias or inflate genotype-phenotype associations, and demonstrate methods that can be used to assess their presence. Using data on educational achievement and parental socioeconomic position as an exemplar, we demonstrate that both heritability and genetic correlation may be biased estimates of the causal contribution of genotype. These results highlight the limitations of genotype-phenotype estimates obtained from samples of unrelated individuals. Use of these methods in combination with family-based designs may offer researchers greater opportunities to explore the mechanisms driving genotype-phenotype associations and identify factors underlying bias in estimates.
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