Evidence map›Paper›PMID 40375105›Full record

ArticleBMC genomics2025

Genome-wide enhancer-gene regulatory maps of liver reveal novel regulatory mechanisms underlying NAFLD pathogenesis.

Ruofan Li, Kaiyan Su, Tianzhun Wu, Li Xu, Wenyu Song, Dandan Sun, Tao Zeng, Jinzhang Chen, Haibei Xin, Yuanfeng Li and 2 more

Abstract read
In one paragraph

Article in BMC genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ruofan Li *Medical School of Chinese People's Liberation Army (PLA), 28 Fuxing Road, 100853, Beijing, China.
Kaiyan Su *State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1,838 North Guangzhou Ave, Guangzhou, Guangdong, 510515, China.
Tianzhun Wu *Department of Digestive Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, China.
Li Xu *Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing, 100029, China.
Wenyu SongState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, China.
Dandan SunDepartment of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Tao ZengMedical School of Chinese People's Liberation Army (PLA), 28 Fuxing Road, 100853, Beijing, China.
Jinzhang ChenState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1,838 North Guangzhou Ave, Guangzhou, Guangdong, 510515, China. chenjinzhang@smu.edu.cn.
Haibei XinDepartment of Hepatobiliary Surgery, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China. xinhaibei@qq.com.
Yuanfeng LiState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, China. liyf_snp@163.com.
Mengya ZangState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 1,838 North Guangzhou Ave, Guangzhou, Guangdong, 510515, China. zangmy@163.com.
Minggen HuMedical School of Chinese People's Liberation Army (PLA), 28 Fuxing Road, 100853, Beijing, China. hmg301@126.com.

Funding

the special project of the key research and development tasks of Xinjiang Uygur autonomous region No. 2022B03005-2
6 · The paper itself

Abstract

introductionNon-alcoholic fatty liver disease (NAFLD) represents the most widespread liver disease globally, ranging from non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH) to fibrosis/cirrhosis, with potential progression to hepatocellular carcinoma (HCC). Genome-wide association studies (GWASs) have identified several single nucleotide polymorphisms (SNPs) associated with NAFLD. However, numerous GWAS signals associated with NAFLD locate in non-coding regions, posing a challenge for interpreting their functional annotation.

resultsIn this study, we utilized the Activity-by-Contact (ABC) model to construct the enhancer-gene maps of liver by integrating epigenomic data from 15 liver tissues and cell lines. We constructed the most comprehensive genome-wide regulatory maps of the liver, identifying 543,486 enhancer-gene connections, including 267,857 enhancers and 16,872 target genes. Enrichment analyses revealed that the ABC SNPs are significantly enriched in active chromatin regions and active chromatin state. By combining the ABC regulatory maps and NAFLD GWAS data, we systematically identified ABC SNPs associated with NAFLD risk. Through the functional annotations, such as pathway enrichment and drug-gene interaction analyses, we identified 6 genes (GGT1, ACTG1, SPP1, EPHA2, PROZ and SHMT1) as candidate NAFLD genes, with SHMT1 previously reported. Among the SNPs connected to the candidate genes, the ABC SNP rs2017869 (odds ratio [OR] for the C allele = 1.10, 95% CI = 1.04-1.16, P = 5.97 × 10

conclusionsOur study provides the most comprehensive ABC regulatory maps of the liver to date. This resource offers a valuable reference for identifying regulatory variants and prioritizing susceptibility genes of liver diseases, such as NAFLD.

Indexed as

Enhancer Elements, GeneticGene Regulatory NetworksLiverNon-alcoholic Fatty Liver DiseaseGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideGenome-wide association studyGGT1Non-alcoholic fatty liver diseaseSingle nucleotide polymorphism

Identifiers

PMID40375105
PMCPMC12082939

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.