Expression quantitative trait loci (eQTL): from population genetics to precision medicine

Zhi Qi Wong; Lian Deng; Alvin Cengnata; Thuhairah Abdul Rahman; Aletza Mohd Ismail; Renee Lay Hong Lim; Shuhua Xu; Boon-Peng Hoh

doi:10.1016/j.jgg.2025.02.003

Volume 52 Issue 4

Apr. 2025

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Article Navigation > Journal of Genetics and Genomics > 2025 > 52(4): 449-459

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Expression quantitative trait loci (eQTL): from population genetics to precision medicine

doi: 10.1016/j.jgg.2025.02.003

a. Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia;
b. State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China;
c. Clinical Pathology Diagnostic Centre Research Laboratory, Faculty of Medicine, Universiti Teknologi MARA, 47000, Malaysia;
d. Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
e. Department of Liver Surgery and Transplantation Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200433, China;
f. Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200433, China;
g. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China;
h. Jiangsu Key Laboratory of Phylogenomics and Comparative Genomics, School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu 221008, China;
i. Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China;
j. Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650223, China;
k. Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, IMU University, Kuala Lumpur 57000, Malaysia

Funds:

This study was supported by the Ministry of Higher Education (MOHE) Malaysia through Fundamental Research Grant Scheme (FRGS) with project code: FRGS/1/2021/STG01/UCSI/01/. SX was funded by the National Natural Science Foundation of China (NSFC) grants 32030020 and 32288101. LD was funded by the NSFC grant 32270665. The authors thank the data owners for agreeing to share the data for our analysis.

Received Date: 2024-11-11
Accepted Date: 2025-02-12
Rev Recd Date: 2025-02-11

Available Online: 2025-07-11

Publish Date: 2025-02-20

Abstract

Abstract

Evidence has shown that differential transcriptomic profiles among human populations from diverse ancestries, supporting the role of genetic architecture in regulating gene expression alongside environmental stimuli. Genetic variants that regulate gene expression, known as expression quantitative trait loci (eQTL), are primarily shaped by human migration history and evolutionary forces, likewise, regulation of gene expression in principle could have been influenced by these events. Therefore, a comprehensive understanding of how human evolution impacts eQTL offers important insights into how phenotypic diversity is shaped. Recent studies, however, suggest that eQTL is enriched in genes that are selectively constrained. Whether eQTL is minimally affected by selective pressures remains an open question and requires comprehensive investigations. In addition, such studies are primarily dominated by the major populations of European ancestry, leaving many marginalized populations underrepresented. These observations indicate there exists a fundamental knowledge gap in the role of genomics variation on phenotypic diversity, which potentially hinders precision medicine. This article aims to revisit the abundance of eQTL across diverse populations and provide an overview of their impact from the population and evolutionary genetics perspective, subsequently discuss their influence on phenomics, as well as challenges and opportunities in the applications to precision medicine.
- eQTL,
- Transcriptomics,
- Genomics,
- Phenomics,
- Population genetics,
- Precision medicine

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References(130)

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