{"doi":"10.1016/j.xpro.2025.103780","title":"Protocol to estimate the heritability of drug response with GxEMM and identify gene-drug interactions with TxEWAS","abstract":"Identifying factors that affect treatment response is a central objective of clinical research. Here, we present a protocol to study the genetic architecture of response to commonly prescribed drugs using gene-context interaction techniques. We describe steps for estimating the heritability of drug response with gene-environment interaction mixed model (GxEMM) and identifying gene-drug interactions with gene-environment interaction transcriptome-wide association study (TxEWAS). While the protocol describes application to drug treatments, this framework can be used to characterize the genetic basis of any covariate’s effect. For complete details on the use and execution of this protocol, please refer to Sadowski et al. 1 • Instructions for installing software and preparing data for analysis • Steps for estimating the heritability of drug response with GxEMM • Steps for identifying gene-drug interactions with TxEWAS Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Identifying factors that affect treatment response is a central objective of clinical research. Here, we present a protocol to study the genetic architecture of response to commonly prescribed drugs using gene-context interaction techniques. We describe steps for estimating the heritability of drug response with gene-environment interaction mixed model (GxEMM) and identifying gene-drug interactions with gene-environment interaction transcriptome-wide association study (TxEWAS). While the protocol describes application to drug treatments, this framework can be used to characterize the genetic basis of any covariate’s effect.","journal":"STAR Protocols","year":2025,"id":540919,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":293288,"name":"Andy Dahl","orcid":null,"position":1,"is_corresponding":false},{"id":24103,"name":"Noah Zaitlen","orcid":"0000-0002-3553-3670","position":2,"is_corresponding":false},{"id":1228359,"name":"Michał Sadowski","orcid":"0000-0002-5998-0432","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40249708","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":[]}