Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.
Cell Genom
; 4(1): 100469, 2024 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-38190103
ABSTRACT
Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genômica
/
Locos de Características Quantitativas
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Idioma:
En
Revista:
Cell Genom
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido