Fine-mapping cellular QTLs with RASQUAL and ATAC-seq.
Nat Genet
; 48(2): 206-13, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-26656845
ABSTRACT
When cellular traits are measured using high-throughput DNA sequencing, quantitative trait loci (QTLs) manifest as fragment count differences between individuals and allelic differences within individuals. We present RASQUAL (Robust Allele-Specific Quantitation and Quality Control), a new statistical approach for association mapping that models genetic effects and accounts for biases in sequencing data using a single, probabilistic framework. RASQUAL substantially improves fine-mapping accuracy and sensitivity relative to existing methods in RNA-seq, DNase-seq and ChIP-seq data. We illustrate how RASQUAL can be used to maximize association detection by generating the first map of chromatin accessibility QTLs (caQTLs) in a European population using ATAC-seq. Despite a modest sample size, we identified 2,707 independent caQTLs (at a false discovery rate of 10%) and demonstrated how RASQUAL and ATAC-seq can provide powerful information for fine-mapping gene-regulatory variants and for linking distal regulatory elements with gene promoters. Our results highlight how combining between-individual and allele-specific genetic signals improves the functional interpretation of noncoding variation.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Sitios de Carácter Cuantitativo
/
Secuenciación de Nucleótidos de Alto Rendimiento
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido