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Nat. Genet., 25 June 2025 | https://doi.org/10.1038/s41588-025-02237-8
Single-cell eQTL analysis identifies genetic variation underlying metabolic dysfunction-associated steatohepatitis
Sung Eun Hong 1, Seon Ju Mun 2, Young Joo Lee 3, Taekyeong Yoo 1, Kyung-Suk Suh 4, Keon Wook Kang 3, Myung Jin Son 2,5, Won Kim 6,7,* & Murim Choi 1,7,*
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
3College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
4Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
3College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
4Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
5Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon, Republic of Korea.
6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
7These authors contributed equally: Won Kim, Murim Choi.
6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
7These authors contributed equally: Won Kim, Murim Choi.
*Corresponding authors: correspondence to Won Kim or Murim Choi
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized for its medical and socioeconomic impacts, driven by diverse genetic and environmental factors. Here, to address the urgent need for individually tailored therapies, we show results from single-cell expression quantitative trait locus (sc-eQTL) analysis on liver biopsies from 25 patients with MASLD and 23 controls. This approach identified over 3,500 sc-eQTLs across major liver cell types and cell-state-interacting eQTLs (ieQTLs) with significant enrichment for disease heritability (for MASLD trait, ieQTL enrichment odds ratio 10.27). We integrated transcription factors as upstream regulators of ieQTLs, revealing 601 functional units (‘quartets’) composed of transcription factors, cell states, SNP components of ieQTL (ieSNPs) and Gene component of ieQTL (ieGenes). From these results, we pinpoint the loss of an eQTL in EFHD1 during hepatocyte maladaptation associated with genotype-specific regulation by FOXO1, further contributing to the risk of MASLD. Our approach underscores the role of eQTL analysis in capturing crucial genetic variations that influence gene expression and clinical outcomes in complex diseases.
논문정보
- Research article
- 2025년 06월 (BRIC 등록일 2025-06-26)
- 국내 연구진
- 의약학 > 유전 및 유전체의학
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