Evidence map›Paper›PMID 40645996›Full record

SynthesisNature communications2025

Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation.

Shuai Yuan, Jie Chen, Xixin Ruan, Yuying Li, Sarah A Abramowitz, Lijuan Wang, Fangyuan Jiang, Ying Xiong, Michael G Levin, Benjamin F Voight and 7 more

Erratum issuedAbstract readMeta-Analysis
In one paragraph

Synthesis in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. NovelBiomedicines · 2026
    Article
  5. Article
  6. Article
  7. Clinical utility of polygenic risk scores in cardiovascular disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
  8. Rare TruncatingGenes · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Multi-omics integration predicts 17 disease incidences in the UK Biobank.medRxiv : the preprint server for health sciences · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Shuai Yuan *Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Shuai.Yuan@Pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0001-5055-5627
Jie Chen *Department of Gastroenterology, Central South University Third Xiangya Hospital, Changsha, Hunan, China.ORCID http://orcid.org/0000-0002-4029-4192
Xixin RuanDepartment of Gastroenterology, Central South University Third Xiangya Hospital, Changsha, Hunan, China.ORCID http://orcid.org/0000-0002-4937-9168
Yuying LiDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-3231-7542
Sarah A AbramowitzDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Lijuan WangSchool of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0002-9797-0753
Fangyuan JiangSchool of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Ying XiongDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-7644-014X
Michael G LevinCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9937-9932
Benjamin F VoightCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6205-9994
Dipender GillDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.ORCID http://orcid.org/0000-0001-7312-7078
Stephen BurgessMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-5365-8760
Agneta ÅkessonUnit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-9594-4140
Karl MichaëlssonMedical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Xue LiSchool of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0001-6880-2577
Scott M DamrauerDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8009-1632
Susanna C LarssonUnit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0118-0341

Funding

Training Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0M
American Heart Association (American Heart Association, Inc.) 24POST1189614NHLBI NIH HHS T32 HL007843Wellcome Trust 225790
6 · The paper itself

Abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia with strong genetic components, yet its underlying molecular mechanisms and potential therapeutic targets remain incompletely understood. We conducted a cross-population genome-wide meta-analysis of 168,007 AF cases and identified 525 loci that met genome-wide significance. Two loci of PITX2 and ZFHX3 genes were identified as shared across populations of different ancestries. Comprehensive gene prioritization approaches reinforced the role of muscle development and heart contraction while also uncovering additional pathways, including cellular response to transforming growth factor-beta. Population-specific genetic correlations uncovered common and unique circulatory comorbidities between Europeans and Africans. Mendelian randomization identified modifiable risk factors and circulating proteins, informing disease prevention and drug development. Integrating genomic data from this cross-population genome-wide meta-analysis with proteomic profiling significantly enhanced AF risk prediction. This study advances our understanding of the genetic etiology of AF while also enhancing risk prediction, prevention strategies, and therapeutic development.

Indexed as

Atrial FibrillationGenome-Wide Association StudyProteomicsAfrican PeopleEuropean PeopleFemaleGenetic Predisposition to DiseaseHomeobox Protein PITX2Homeodomain ProteinsHumansMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk FactorsTranscription FactorsHomeobox Protein PITX2Homeodomain ProteinsTranscription FactorsZFHX3 protein, human

Identifiers

PMID40645996
PMCPMC12254421

What Socratic holds

Textmetadata
LicenceCC BY
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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.