{"doi":"10.1101/2021.03.08.434451","title":"Identification of putative causal loci in whole-genome sequencing data via knockoff statistics","abstract":"Abstract The analysis of whole-genome sequencing studies is challenging due to the large number of rare variants in noncoding regions and the lack of natural units for testing. We propose a statistical method to detect and localize rare and common risk variants in whole-genome sequencing studies based on a recently developed knockoff framework. It can (1) prioritize causal variants over associations due to linkage disequilibrium thereby improving interpretability; (2) help distinguish the signal due to rare variants from shadow effects of significant common variants nearby; (3) integrate multiple knockoffs for improved power, stability and reproducibility; and (4) flexibly incorporate state-of-the-art and future association tests to achieve the benefits proposed here. In applications to whole-genome sequencing data from the Alzheimer’s Disease Sequencing Project (ADSP) and COPDGene samples from NHLBI Trans-Omics for Precision Medicine (TOPMed) Program we show that our method compared with conventional association tests can lead to substantially more discoveries.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216435,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":669572,"name":"Linxi Liu","orcid":"0000-0003-0507-0510","position":1,"is_corresponding":false},{"id":530006,"name":"Chen Wang","orcid":"0000-0001-9127-0054","position":2,"is_corresponding":false},{"id":273391,"name":"Yann Le Guen","orcid":"0000-0001-6649-8364","position":3,"is_corresponding":false},{"id":317414,"name":"Justin Lee","orcid":"0000-0001-8269-7494","position":4,"is_corresponding":false},{"id":24965,"name":"Stephanie M. Gogarten","orcid":"0000-0002-7231-9745","position":5,"is_corresponding":false},{"id":584864,"name":"Fred Lu","orcid":"0000-0003-1026-5734","position":6,"is_corresponding":false},{"id":52,"name":"Stephen B. Montgomery","orcid":"0000-0002-5200-3903","position":7,"is_corresponding":false},{"id":108738,"name":"Hua Tang","orcid":"0000-0002-0177-8864","position":8,"is_corresponding":false},{"id":25018,"name":"Edwin K. Silverman","orcid":"0000-0002-3641-3822","position":9,"is_corresponding":false},{"id":218537,"name":"Michael H. Cho","orcid":"0000-0002-4907-1657","position":10,"is_corresponding":false},{"id":32598,"name":"Michael D. Greicius","orcid":"0000-0002-5462-9037","position":11,"is_corresponding":false},{"id":104430,"name":"Iuliana Ionita‐Laza","orcid":"0000-0002-9001-2026","position":12,"is_corresponding":false},{"id":481645,"name":"Zihuai He","orcid":"0000-0002-8220-4183","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:53:11.245932Z","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":[]}