{"doi":"10.26508/lsa.202201446","title":"chromMAGMA: regulatory element-centric interrogation of risk variants","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.","journal":"Life Science Alliance","year":2022,"id":292571,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":404867,"name":"Anamay Shetty","orcid":"0000-0003-0564-7236","position":1,"is_corresponding":false},{"id":231119,"name":"Eileen Dareng","orcid":"0000-0003-0802-419X","position":2,"is_corresponding":false},{"id":21839,"name":"Jonathan P. Tyrer","orcid":"0000-0003-3724-4757","position":3,"is_corresponding":false},{"id":561522,"name":"Xianzhi Lin","orcid":"0000-0001-9802-9896","position":4,"is_corresponding":false},{"id":33596,"name":"Paul D.P. Pharoah","orcid":"0000-0001-8494-732X","position":5,"is_corresponding":false},{"id":321179,"name":"Rosario I. Corona","orcid":"0000-0003-0470-4446","position":6,"is_corresponding":false},{"id":249315,"name":"Siddhartha Kar","orcid":"0000-0002-2314-1426","position":7,"is_corresponding":false},{"id":321180,"name":"Kate Lawrenson","orcid":"0000-0002-6469-2515","position":8,"is_corresponding":false},{"id":321176,"name":"Robbin Nameki","orcid":"0000-0002-2538-5694","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T00:30:46.209549Z","pmid":"35777959","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}