ArticleGenetic epidemiology2018
An ancestry-based approach for detecting interactions.
Article in Genetic epidemiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Hidden structure in polygenic scores and the challenge of disentangling ancestry interactions in admixed populations.Genetics · 2025Article
- A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic interaction effects.Nature genetics · 2025Article
- Epistatic contributions to human traits via transcription factor mechanisms.medRxiv : the preprint server for health sciences · 2025Article
- Efficient and accurate framework for genome-wide gene-environment interaction analysis in large-scale biobanks.Nature communications · 2025Article
- Haplotype analysis incorporating ancestral origins identified novel genetic loci associated with chicken body weight using an advanced intercross line.Genetics, selection, evolution : GSE · 2024Article
- Understanding genetic variants in context.eLife · 2024Article
- Gene-environment interactions in human health.Nature reviews. Genetics · 2024Review
- Strategies for the Genomic Analysis of Admixed Populations.Annual review of biomedical data science · 2023Review
- A model and test for coordinated polygenic epistasis in complex traits.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Early Life Adversity and Polygenic Risk for High Fasting Insulin Are Associated With Childhood Impulsivity.Frontiers in neuroscience · 2021Article
- Admixed Populations Improve Power for Variant Discovery and Portability in Genome-Wide Association Studies.Frontiers in genetics · 2021Article
- Modeling epistasis in mice and yeast using the proportion of two or more distinct genetic backgrounds: Evidence for "polygenic epistasis".PLoS genetics · 2020Article
- Mixed-model admixture mapping identifies smoking-dependent loci of lung function in African Americans.European journal of human genetics : EJHG · 2020Article
- Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.NPJ genomic medicine · 2019Article
- The clinical imperative for inclusivity: Race, ethnicity, and ancestry (REA) in genomics.Human mutation · 2018Article
- Genetic Ancestry for Sleep Research: Leveraging Health Inequalities to Identify Causal Genetic Variants.Chest · 2018Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundEpistasis and gene-environment interactions are known to contribute significantly to variation of complex phenotypes in model organisms. However, their identification in human association studies remains challenging for myriad reasons. In the case of epistatic interactions, the large number of potential interacting sets of genes presents computational, multiple hypothesis correction, and other statistical power issues. In the case of gene-environment interactions, the lack of consistently measured environmental covariates in most disease studies precludes searching for interactions and creates difficulties for replicating studies.
resultsIn this work, we develop a new statistical approach to address these issues that leverages genetic ancestry, defined as the proportion of ancestry derived from each ancestral population (e.g., the fraction of European/African ancestry in African Americans), in admixed populations. We applied our method to gene expression and methylation data from African American and Latino admixed individuals, respectively, identifying nine interactions that were significant at P<5×10-8. We show that two of the interactions in methylation data replicate, and the remaining six are significantly enriched for low P-values (P<1.8×10-6).
conclusionWe show that genetic ancestry can be a useful proxy for unknown and unmeasured covariates in the search for interaction effects. These results have important implications for our understanding of the genetic architecture of complex traits.
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