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Integrated multi-omics profiling identifies genetic loci of African swine fever resistance in pigs.

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Title: Integrated multi-omics profiling identifies genetic loci of African swine fever resistance in pigs.
Authors: Ye X; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Xie Q; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Cao C; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Liu S; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China., Sun W; Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, Shandong 250100, China., Zhang Z; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.; Hainan Institute, Zhejiang University, Yongyou Industrial Park, Yazhou Bay Sci-Tech City, Sanya 572000, China., Wang Q; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.; Hainan Institute, Zhejiang University, Yongyou Industrial Park, Yazhou Bay Sci-Tech City, Sanya 572000, China., Pan Y; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.; Hainan Institute, Zhejiang University, Yongyou Industrial Park, Yazhou Bay Sci-Tech City, Sanya 572000, China., Wang Z; Zhejiang Key Laboratory of Nutrition and Breeding for High-Quality Animal Products, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.; Hainan Institute, Zhejiang University, Yongyou Industrial Park, Yazhou Bay Sci-Tech City, Sanya 572000, China.
Source: GigaScience [Gigascience] 2026 Jan 21; Vol. 15.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Oxford University Press Country of Publication: United States NLM ID: 101596872 Publication Model: Print Cited Medium: Internet ISSN: 2047-217X (Electronic) Linking ISSN: 2047217X NLM ISO Abbreviation: Gigascience Subsets: MEDLINE
Imprint Name(s): Publication: 2017- : New York : Oxford University Press
Original Publication: London : BioMed Central
MeSH Terms: African Swine Fever*/genetics , African Swine Fever*/virology , Disease Resistance*/genetics , Genetic Loci*, Genomics/methods ; Animals ; Swine ; Genome-Wide Association Study ; Multiomics ; Gene Expression Profiling ; Polymorphism, Single Nucleotide ; African Swine Fever Virus ; Quantitative Trait Loci ; Transcriptome ; Genetic Predisposition to Disease
Abstract: Background: African swine fever (ASF) remains a persistent threat to global pig production, with no licensed vaccines or effective treatments available. Observations of surviving individuals within low-virulence infected herds suggest that host genetic resistance plays a crucial role.
Results: Here, we present a multi-dimensional integrative analysis to uncover host genomic variants associated with ASF resistance. Combining genome-wide association studies (GWAS), genetic differentiation, and functional genomic approaches, including TWAS, SMR, colocalization, and Bayesian network GWAS, we prioritized 135 high-priority candidate resistance genes from an initial gene set of 1,102 candidates. These prioritized genes are enriched in immune-related pathways, such as chemokine signaling and IL-15-mediated activation. Heritability enrichment and transcriptomic analyses further revealed tissue- and cell-type-specific expression patterns, particularly in peripheral immune organs and pulmonary alveolar macrophages. Dynamic infection-responsive genes, including CXCL10, CXCL11, and IL15, exhibited robust antiviral signatures, which highlighted Mac_CD163 as key cellular mediators in the immune response to ASF. Moreover, multiple genes (such as SOS1, FCGR2B, FCGR3) converged on the PI3K-AKT and Fcγ receptor signaling axes pathways, underscoring their functional importance. Finally, we developed a polygenic resistance score using 40 prioritized independent SNPs, which effectively discriminates phenotypic outcomes and showed a positive correlation with health traits such as platelet distribution width.
Conclusions: These findings provided a genomic foundation for the precision breeding of ASF-resistant pigs and inform host-targeted disease control strategies.
(© The Author(s) 2026. Published by Oxford University Press on behalf of GigaScience.)
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Grant Information: 2021LZGC001 Agricultural Improved Varieties Project in Shandong Province of China; 31941007 National Natural Science Foundation of China
Contributed Indexing: Keywords: African swine fever; disease resistance; host genetics; multi-omics; pig breeding
Molecular Sequence: BioProject PRJNA1290525, PRJCA057587
Entry Date(s): Date Created: 20260530 Date Completed: 20260625 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13289747
DOI: 10.1093/gigascience/giag066
PMID: 42216858
Database: MEDLINE
Description
ISSN:2047-217X
DOI:10.1093/gigascience/giag066