ArticleAmerican journal of human genetics2019
On Using Local Ancestry to Characterize the Genetic Architecture of Human Traits: Genetic Regulation of Gene Expression in Multiethnic or Admixed Populations.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Validation of serotonin transporter mRNA as a quantitative biomarker of heavy drinking and its comparison to ethyl glucuronide/ethyl sulfate: A randomized, double-blind, crossover trial.Alcoholism, clinical and experimental research · 2022Trial
- OmiGA for ultra-efficient molecular quantitative trait loci mapping.Nature communications · 2026Article
- Article
- Local ancestry-informed GWAS of warfarin dose requirement in African Americans identifies a CYP2C19 splicing QTL.American journal of human genetics · 2025Article
- Phase-free local ancestry inference mitigates the impact of switch errors on phase-based methods.G3 (Bethesda, Md.) · 2025Article
- Opportunities and challenges of local ancestry in genetic association analyses.American journal of human genetics · 2025Review
- Equitable machine learning counteracts ancestral bias in precision medicine.Nature communications · 2025Article
- Characterizing substructure via mixture modeling in large-scale genetic summary statistics.American journal of human genetics · 2025Article
- Integrating multi-layered biological priors to improve genomic prediction accuracy in beef cattle.Biology direct · 2024Article
- RFMix-reader: Accelerated reading and processing for local ancestry studies.bioRxiv : the preprint server for biology · 2024Article
- Characterizing substructure via mixture modeling in large-scale genetic summary statistics.bioRxiv : the preprint server for biology · 2024Article
- Improved multi-ancestry fine-mapping identifiesmedRxiv : the preprint server for health sciences · 2024Article
- The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Article
- Transcriptome-Wide Association Studies (TWAS): Methodologies, Applications, and Challenges.Current protocols · 2024Article
- Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape.Nature communications · 2023Review
- Impact of cross-ancestry genetic architecture on GWASs in admixed populations.American journal of human genetics · 2023Article
- Limitations of principal components in quantitative genetic association models for human studies.eLife · 2023Article
- MATS: a novel multi-ancestry transcriptome-wide association study to account for heterogeneity in the effects of cis-regulated gene expression on complex traits.Human molecular genetics · 2023Article
- Comparative Genomic and Transcriptomic Analyses Reveal the Impacts of Genetic Admixture in Kazaks, Uyghurs, and Huis.Molecular biology and evolution · 2023Article
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3 authors.
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Abstract
Understanding the nature of the genetic regulation of gene expression promises to advance our understanding of the genetic basis of disease. However, the methodological impact of the use of local ancestry on high-dimensional omics analyses, including, most prominently, expression quantitative trait loci (eQTL) mapping and trait heritability estimation, in admixed populations remains critically underexplored. Here, we develop a statistical framework that characterizes the relationships among the determinants of the genetic architecture of an important class of molecular traits. We provide a computationally efficient approach to local ancestry analysis in eQTL mapping while increasing control of type I and type II error over traditional approaches. Applying our method to National Institute of General Medical Sciences (NIGMS) and Genotype-Tissue Expression (GTEx) datasets, we show that the use of local ancestry can improve eQTL mapping in admixed and multiethnic populations, respectively. We estimate the trait variance explained by ancestry by using local admixture relatedness between individuals. By using simulations of diverse genetic architectures and degrees of confounding, we show improved accuracy in estimating heritability when accounting for local ancestry similarity. Furthermore, we characterize the sparse versus polygenic components of gene expression in admixed individuals. Our study has important methodological implications for genetic analysis of omics traits across a range of genomic contexts, from a single variant to a prioritized region to the entire genome. Our findings highlight the importance of using local ancestry to better characterize the heritability of complex traits and to more accurately map genetic associations.
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