Evidence map›Paper›PMID 40948743›Full record

SynthesisFrontiers in immunology2025

Genetic architecture of primary biliary cholangitis: strong evidence for HLA and non-HLA risk loci.

Min Zhang, Liang Lyu, Liang Ge, Yizhou Wang, Dongqing Gu

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

5 authors.

Min Zhang *Department of Sleep and Psychology, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.
Liang Lyu *Department of College of Medical Informatics, Chongqing Medical University, Chongqing, China.
Liang GeDepartment of Laboratory of Infection and Immunity, West China School of Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
Yizhou WangDepartment of Pathology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, China.
Dongqing GuDepartment of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Despite extensive genetic studies investigating primary biliary cholangitis (PBC), the mechanistic basis of risk-associated variants remains poorly understood. To address this gap, we performed a systematic evaluation of cumulative evidence linking genetic variants to PBC susceptibility. Methods: A comprehensive search was conducted to identify published studies on the association between genetic variants and PBC risk. Specifically, separate analyses were conducted for genome-wide association studies (GWASs) and candidate-gene association studies to address potential heterogeneity arising from differences in study design. Meta-analyses were performed to calculate pooled odds ratio (OR) and 95% confidence interval (CI) for the candidate-gene association studies. Significant associations were further graded using Venice criteria and false-positive report probability (FPRP) tests. Functional annotation, pathway enrichment, and phenome-wide analyses were performed to elucidate biological relevance. Results: Overall, we included 105 articles involving 71,031 cases and 140,499 controls. Meta-analyses were conducted for 70 variants across 33 genes. Among these, 44 variants were identified as significantly associated with PBC risk, comprising 30 HLA variants and 14 non-HLA variants. Separately, published GWAS have reported 115 significant variants. Nine variants (DQA1*0401, DQB1*0301, DQB1*0402, DQB1*0602, DRB1*08, DRB1*0803, DRB1*11, DRB1*1101, and rs7574865) were identified by both approaches. Additionally, meta-analyses of candidate-gene association studies provided strong evidence supporting the association of eight further variants (A*3303, B*4403, DPB1*0201, DQB1*0401, rs231725, rs231775, rs1544410, and rs9303277) with PBC at the genome-wide significance level ( Conclusion: This study provides the most comprehensive synopsis to date of PBC's genetic architecture, highlighting robust HLA and non-HLA risk loci. Systematic review registration: https:///www.crd.york.ac.uk/PROSPERO/view/CRD42021282146, identifier CRD42021282146.

Indexed as

Genetic LociGenetic Predisposition to DiseaseHLA AntigensLiver Cirrhosis, BiliaryGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRisk FactorsHLA Antigenscumulative evidencefunctional annotationgenetic architecturemeta-analysisphenome-wide analysisprimary biliary cholangitisvariants

Identifiers

PMID40948743
PMCPMC12425925

What Socratic holds

Textmetadata
LicenceCC BY
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.