Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes
Hongru Li1, Jingyi Zhao1, Jinglan Dai1
1Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Nature Communications
|April 24, 2025
Summary
This study identified 113 genetic signals for C-reactive protein (CRP) levels across diverse ancestries, revealing new insights into systemic inflammation regulation. It implicated 151 genes, including 55 novel ones, impacting CRP and related diseases.
Area of Science:
- Genetics
- Immunology
- Population Genetics
Background:
- C-reactive protein (CRP) is a key systemic inflammation marker.
- Previous genetic studies primarily focused on European populations, limiting understanding of global genetic architecture.
Purpose of the Study:
- To conduct a multi-ancestry, sequencing-based genome-wide association study (seqGWAS) to identify novel genetic associations for CRP levels.
- To explore the genetic regulation of CRP across diverse global populations.
Main Methods:
- A large-scale meta-analysis of seqGWAS in discovery (N≈476k) and replication (N≈36k) sets across European, African, Asian, and Hispanic ancestries.
- Fine-mapping and functional annotation using credible sets, Polygenic Priority Score (PoPS), and gene-based analyses.
Main Results:
- Identified 113 independent association signals for CRP levels, with 3 European-specific loci.
- Fine-mapping pinpointed 19 signals within credible sets, enriched in blood tissues and exonic regions.
- Implicated 151 potential CRP-regulating genes, 55 newly reported, with 17 genes and 4 proteins showing causal links to CRP-related pathologies.
Conclusions:
- This multi-ancestry study significantly expands the known genetic landscape of CRP levels.
- Identifies novel genes and provides functional insights into CRP regulation and its association with disease.
- Highlights the importance of diverse populations in genetic discovery for complex traits.
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