In a recent Genes & Diseases review, researchers from Harbin Medical University and Zhejiang University provide an overview of eQTLs, their identification and analysis, development during different physiological periods, existing data resources, and their application in four typical diseases.
eQTLs modulate gene expression through several molecular mechanisms, including altering transcription factor binding affinity or chromatin accessibility when located within transcription initiation regions, or by directly influencing the activity of the encoded protein when located in coding regions, and via intermediary regulatory molecules, such as microRNAs.
scRNA-seq has facilitated the identification of crucial tissue-specific and cell-type-specific eQTLs, highlighting the critical role of cellular context in genetic regulation and providing deeper insights into disease etiology, such as autoimmune diseases.

The review describes the data types used in eQTL analysis—including raw genotype data, gene expression data, covariate data, and location files—while discussing the tools—MatrixeQTL, FastQTL, and QTLtools. Apart from these scRNA-seq-based tools—eQTLsingle method, SURGE, and Cell Regulatory Map—cell-type-specific eQTL (ct-eQTL) and single-nucleotide variant eQTLs are also used for eQTL identification.
eQTLs are crucial for elucidating the functional relationship between GWAS-identified genetic variants in non-coding regions and the associated complex traits, enabling causal inference methods, such as TWAS and Mendelian randomization. eCAVIAR, SMR, XGR, and OmicKriging are some of the tools used for integrating eQTL and GWAS data.

The review then summarizes the development of eQTL research over the microarray method, high-throughput sequencing period, post-genome period, and single-cell sequencing period. It also lists the common data sources—GTEx (V8), eQTLGen, eQTL Catalogue, OneK1K, scQTLbase, SingleQ, PancanQTL, Blood eQTL Browser, EyeGEx, and ImmuNexUT.

eQTL analysis has provided molecular insights into the pathogenesis of diseases such as rheumatoid arthritis (RA), type 2 diabetes (T2D), breast cancer, and schizophrenia (SZ), by elucidating the precise molecular regulatory mechanisms of risk variants. For RA, eQTLs identified novel genes (e.g., JAZF1, PTPN22) and mechanisms, such as rs142845557, regulating chromatin accessibility in synovial tissue. In T2D, eQTLs were crucial for understanding the impact of genetic variants on islet cell function and insulin secretion (e.g., PFKM, KCNA6), providing insights beyond standard GWAS risk loci. For breast cancer, eQTL analysis revealed risk loci regulating key genes (ESR1, MYC) and affecting promoter activity of cancer-related genes. Similarly, in SZ, eQTLs, often combined with single-cell RNA sequencing, facilitated the identification of novel risk genes (ALMS1, SNX19) and highlighted the role of specific brain regions and cell types (e.g., inhibitory neurons) in pathogenesis, consistently underscoring the power of eQTLs as functional connectors in understanding complex disease etiology.

In conclusion, this review provides a comprehensive understanding of eQTLs, tools used for their identification and analysis, and their potential in understanding the molecular pathogenesis of diseases, such as RA, T2D, breast cancer, and schizophrenia.

Reference
Title of the original paper: eQTL analysis: A bridge from genome to mechanism

Journal: Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

DOI: https://doi.org/10.1016/j.gendis.2025.101850

Funding Information:

• Program for Young Talents of Basic Research in Universities of Heilongjiang Province, China (No. YQJH2023036)
• National Natural Science Foundation of China (No. 31970651, No. 92046018, No. 81601422, No. 81600403)
• Mathematical Tianyuan Fund of the National Natural Science Foundation of China (No. 12026414)
• Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (No. LBY24H170001)
• Marshal Initiative Funding of Harbin Medical University, Heilongjiang, China (No. HMUMIF-22010).

# # # # # #

Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Scopus CiteScore: 8.4
Impact Factor: 9.4

# # # # # #


More information: https://www.keaipublishing.com/en/journals/genes-and-diseases/
Editorial Board: https://www.keaipublishing.com/en/journals/genes-and-diseases/editorial-board/
All issues and articles in press are available online in ScienceDirect (https://www.sciencedirect.com/journal/genes-and-diseases).
Submissions to Genes & Disease may be made using Editorial Manager (https://www.editorialmanager.com/gendis/default.aspx).

Print ISSN: 2352-4820
eISSN: 2352-3042
CN: 50-1221/R


Contact Us: editor@genesndiseases.cn
X (formerly Twitter): @GenesNDiseases (https://x.com/GenesNDiseases)