{"doi":"10.21203/rs.2.14850/v2","title":"A New Efficient Method to Detect Genetic Interactions for Lung Cancer GWAS","abstract":"Abstract Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset. Methods: To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data. Results: Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR = 1.24, P = 3.15 x 10 -15 ), as the top marker to predict age of lung cancer onset. Conclusions: From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.","journal":"Research Square","year":2020,"id":134614,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":15499,"name":"Xuemei Ji","orcid":"0000-0001-7416-9122","position":1,"is_corresponding":false},{"id":369825,"name":"Siting Li","orcid":"0000-0002-8292-1393","position":2,"is_corresponding":false},{"id":15498,"name":"Xiangjun Xiao","orcid":null,"position":3,"is_corresponding":false},{"id":97265,"name":"Dakai Zhu","orcid":"0000-0002-1938-9947","position":4,"is_corresponding":false},{"id":334594,"name":"Eric J. Duell","orcid":"0000-0001-5256-0163","position":5,"is_corresponding":false},{"id":251842,"name":"David C. Christiani","orcid":"0000-0002-0301-0242","position":6,"is_corresponding":false},{"id":251848,"name":"Matthew B. Schabath","orcid":"0000-0003-3241-3216","position":7,"is_corresponding":false},{"id":251837,"name":"Susanne M. Arnold","orcid":"0000-0001-6542-9551","position":8,"is_corresponding":false},{"id":251850,"name":"Shanbeh Zienolddiny","orcid":"0000-0001-9747-9625","position":9,"is_corresponding":false},{"id":251839,"name":"Hans Brunnström","orcid":"0000-0001-7402-138X","position":10,"is_corresponding":false},{"id":108539,"name":"Olle Melander","orcid":"0000-0002-2581-484X","position":11,"is_corresponding":false},{"id":382208,"name":"Mark Thornquist","orcid":null,"position":12,"is_corresponding":false},{"id":315572,"name":"Todd A. MacKenzie","orcid":"0000-0002-0215-2003","position":13,"is_corresponding":false},{"id":5679,"name":"Christopher I. Amos","orcid":"0000-0002-8540-7023","position":14,"is_corresponding":false},{"id":19642,"name":"Jiang Gui","orcid":"0000-0001-5377-8914","position":15,"is_corresponding":false},{"id":381146,"name":"Jennifer Luyapan","orcid":"0000-0001-6040-6860","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-18T23:16:24.540681Z","pmid":null,"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":[]}