chromMAGMA: regulatory element-centric interrogation of risk variants.
Life Sci Alliance
; 5(10)2022 10.
Article
en En
| MEDLINE
| ID: mdl-35777959
ABSTRACT
Candidate causal risk variants from genome-wide association studies reside almost exclusively in noncoding regions of the genome and innovative approaches are necessary to understand their biological function. Multi-marker analysis of genomic annotation (MAGMA) is a widely used program that nominates candidate risk genes by mapping single-nucleotide polymorphism summary statistics from genome-wide association studies to gene bodies. We augmented MAGMA to create chromatin-MAGMA (chromMAGMA), a method to nominate candidate risk genes based on the presence of risk variants within noncoding regulatory elements (REs). We applied chromMAGMA to a genetic susceptibility dataset for epithelial ovarian cancer (EOC), a rare gynecologic malignancy characterized by high mortality. This identified 155 unique candidate EOC risk genes across five EOC histotypes; 83% (105/127) of high-grade serous ovarian cancer risk genes had not previously been implicated in this EOC histotype. Risk genes nominated by chromMAGMA converged on mRNA splicing and transcriptional dysregulation pathways. chromMAGMA is a pipeline that nominates candidate risk genes through a gene regulation-focused approach and helps interpret the biological mechanism of noncoding risk variants for complex diseases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Secuencias Reguladoras de Ácidos Nucleicos
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Life Sci Alliance
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos