{"doi":"10.7554/elife.90459","title":"Discovering non-additive heritability using additive GWAS summary statistics","abstract":"LD score regression (LDSC) is a method to estimate narrow-sense heritability from genome-wide association study (GWAS) summary statistics alone, making it a fast and popular approach. In this work, we present interaction-LD score (i-LDSC) regression: an extension of the original LDSC framework that accounts for interactions between genetic variants. By studying a wide range of generative models in simulations, and by re-analyzing 25 well-studied quantitative phenotypes from 349,468 individuals in the UK Biobank and up to 159,095 individuals in BioBank Japan, we show that the inclusion of a cis -interaction score (i.e. interactions between a focal variant and proximal variants) recovers genetic variance that is not captured by LDSC. For each of the 25 traits analyzed in the UK Biobank and BioBank Japan, i-LDSC detects additional variation contributed by genetic interactions. The i-LDSC software and its application to these biobanks represent a step towards resolving further genetic contributions of sources of non-additive genetic effects to complex trait variation.","journal":"eLife","year":2024,"id":434145,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307840,"name":"Gregory Darnell","orcid":"0000-0003-0425-940X","position":1,"is_corresponding":false},{"id":1240292,"name":"Dana Udwin","orcid":"0000-0001-8805-0958","position":2,"is_corresponding":false},{"id":1236084,"name":"Julian Stamp","orcid":"0000-0003-3014-6249","position":3,"is_corresponding":false},{"id":65300,"name":"Arbel Harpak","orcid":"0000-0002-3655-748X","position":4,"is_corresponding":false},{"id":301976,"name":"Sohini Ramachandran","orcid":"0000-0002-9588-7964","position":5,"is_corresponding":false},{"id":72592,"name":"Lorin Crawford","orcid":"0000-0003-0178-8242","position":6,"is_corresponding":false},{"id":87235,"name":"Samuel Pattillio Smith","orcid":"0000-0002-6269-0276","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:59:53.957667Z","pmid":"38913556","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":[]}