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Thromb Haemost
DOI: 10.1055/a-2504-0903
Stroke, Systemic or Venous Thromboembolism

Long-Chain Polysaturated Fatty Acid in Atrial Fibrillation–Associated Stroke: Lipidomic-GWAS Study

Youngae Jung   *
1   Integrated Metabolomics Research Group/Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
,
Beomsu Kim   *
2   Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
,
Chi Kyung Kim
3   Department of Neurology, Korea University Guro Hospital, Korea University, Seoul, Republic of Korea
,
Hong-Hee Won
2   Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
,
Su-Hyun Chae
1   Integrated Metabolomics Research Group/Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
4   Department of Chemistry, Sungkyunkwan University, Suwon, Republic of Korea
,
Kyungmi Oh
3   Department of Neurology, Korea University Guro Hospital, Korea University, Seoul, Republic of Korea
,
Min-Jeong Shin
5   Department of Public Health Sciences, Korea University, Seoul, Republic of Korea
,
Geum-Sook Hwang 
1   Integrated Metabolomics Research Group/Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
6   College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
,
Woo-Keun Seo 
7   Department of Neurology, Samsung Medical Center, Sungkyunkwan University and Department of Digital Health, SAIHST, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
› Author Affiliations Funding This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2023-00265393, 2022M3H9A2096189) and Korea Basic Science Institute (No. A423200).
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Abstract

Background and Purpose

This study aimed to explore the relationship between lipidomic domains, particularly free fatty acids (FFAs), and the presence of atrial fibrillation (AF) in patients with acute stroke, and to identify mechanisms of AF-associated stroke through genetic studies.

Methods

A total of 483 stroke patients without AF (n = 391) and with AF (n = 92) were selected from a prospectively collected stroke registry. Lipidomic profiling was conducted, and the lipid components associated with AF were explored using fold-change analyses and clustering. Genotyping was conducted through trait comparison. Colocalization was also performed.

Results

Among the lipidomic domains, the free fatty acid (FFA) class was positively associated with AF. Long-chain fatty acids with 14 to 24 carbons and unsaturated FFAs distinguished AF. Clustering analysis based on FFAs revealed differences in AF proportion across groups. Genome-wide association study (GWAS) identified two loci associated with clustered groups of FFA metabolites: near MIR548F3 associated with FFA 20:1, FFA 20:2, FFA 22:5, and FFA 22:6; and near RPL37A associated with FFA 22:5 and FFA 22:6. These loci were associated with increased fibrinogen levels. In the GWAS for the FFA metabolite, quantitative trial locus analysis, loci near rs28456 and rs3770088, and FFA 20:4-QTLs were co-localized with the eQTLs of FADS2, a gene involved in the peroxisome proliferator-activated receptor gamma-related signaling pathway, in the whole blood, left ventricle, and atrial appendage tissue.

Conclusion

Elevated FFA levels, especially those of long-chain unsaturated FFAs, are strongly associated with AF-associated stroke. This relationship is regulated by the peroxisome proliferator-activated receptor (PPAR) gamma-related signaling pathway.

Keywords

atrial fibrillation - stroke - lipidomics - genome-wide association study - free fatty acids - peroxisome proliferator-activated receptor gamma

* Two authors equally contributed as the first authors in this study.


Supplementary Material



Publication History

Received: 12 July 2024

Accepted: 16 December 2024

Accepted Manuscript online:
18 December 2024

Article published online:
24 March 2025

© 2025. Thieme. All rights reserved.

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Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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