Akademska digitalna zbirka SLovenije - logo
E-viri
Celotno besedilo
Recenzirano Odprti dostop
  • chromMAGMA: regulatory elem...
    Nameki, Robbin; Shetty, Anamay; Dareng, Eileen; Tyrer, Jonathan; Lin, Xianzhi; Pharoah, Paul; Corona, Rosario I; Kar, Siddhartha; Lawrenson, Kate

    Life science alliance, 10/2022, Letnik: 5, Številka: 10
    Journal Article

    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.