{"doi":"10.1101/2021.08.03.453690","title":"Transcriptome-wide association study in UK Biobank Europeans identifies associations with blood cell traits","abstract":"Abstract Previous genome-wide association studies (GWAS) of hematological traits have identified over 10,000 distinct trait-specific risk loci, but the underlying causal mechanisms at these loci remain incompletely characterized. We performed a transcriptome-wide association study (TWAS) of 29 hematological traits in 399,835 UK Biobank (UKB) participants of European ancestry using gene expression prediction models trained from whole blood RNA-seq data in 922 individuals. We discovered 557 TWAS signals associated with hematological traits distinct from previously discovered GWAS variants, including 10 completely novel gene-trait pairs corresponding to 9 unique genes. Among the 557 associations, 301 were available for replication in a cohort of 141,286 participants of European ancestry from the Million Veteran Program (MVP). Of these 301 associations, 199 replicated at a nominal threshold ( α = 0.05) and 108 replicated at a strict Bonferroni adjusted threshold ( α = 0.05/301). Using our TWAS results, we systematically assigned 4,261 out of 16,900 previously identified hematological trait GWAS variants to putative target genes. Compared to coloc , our TWAS results show reduced specificity and increased sensitivity to assign variants to target genes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":219179,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"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":0.8395,"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":696670,"name":"Sanan Venkatesh","orcid":"0000-0002-3094-2731","position":1,"is_corresponding":false},{"id":108707,"name":"Manuel Tardáguila","orcid":"0000-0001-7812-604X","position":2,"is_corresponding":false},{"id":254652,"name":"Jia Wen","orcid":"0000-0003-3273-7704","position":3,"is_corresponding":false},{"id":108735,"name":"Jonathan D. Rosen","orcid":"0000-0001-6396-4219","position":4,"is_corresponding":false},{"id":567627,"name":"Amanda L. Tapia","orcid":"0000-0001-7348-7372","position":5,"is_corresponding":false},{"id":11263,"name":"Quan Sun","orcid":"0000-0001-8324-2803","position":6,"is_corresponding":false},{"id":11261,"name":"Mariaelisa Graff","orcid":"0000-0001-6380-1735","position":7,"is_corresponding":false},{"id":108702,"name":"Dragana Vuckovic","orcid":"0000-0001-9343-6142","position":8,"is_corresponding":false},{"id":22003,"name":"Guillaume Lettre","orcid":"0000-0002-7740-3399","position":9,"is_corresponding":false},{"id":17323,"name":"Vijay G. Sankaran","orcid":"0000-0003-0044-443X","position":10,"is_corresponding":false},{"id":25010,"name":"Alex P. Reiner","orcid":"0000-0002-1427-4470","position":11,"is_corresponding":false},{"id":24551,"name":"Nicole Soranzo","orcid":"0000-0003-1095-3852","position":12,"is_corresponding":false},{"id":108708,"name":"Jennifer E. Huffman","orcid":"0000-0002-9672-2491","position":13,"is_corresponding":false},{"id":1200,"name":"Georgios Voloudakis","orcid":"0000-0002-5729-632X","position":14,"is_corresponding":false},{"id":1203,"name":"Panos Roussos","orcid":"0000-0002-4640-6239","position":15,"is_corresponding":false},{"id":11262,"name":"Laura M. Raffield","orcid":"0000-0002-7892-193X","position":16,"is_corresponding":false},{"id":24805,"name":"Yun Li","orcid":"0000-0002-9275-4189","position":17,"is_corresponding":false},{"id":563198,"name":"Bryce Rowland","orcid":"0000-0002-8900-6905","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:33.915158Z","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":[]}