TY - JOUR T1 - chromMAGMA: regulatory element-centric interrogation of risk variants JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201446 VL - 5 IS - 10 SP - e202201446 AU - Robbin Nameki AU - Anamay Shetty AU - Eileen Dareng AU - Jonathan Tyrer AU - Xianzhi Lin AU - The Ovarian Cancer Association Consortium AU - Paul Pharoah AU - Rosario I Corona AU - Siddhartha Kar AU - Kate Lawrenson Y1 - 2022/10/01 UR - https://www.life-science-alliance.org/content/5/10/e202201446.abstract N2 - 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. ER -