{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:03:22Z","timestamp":1784228602607,"version":"3.55.0"},"reference-count":113,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6808","funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008184","name":"COPD Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008184","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008925","name":"American Asthma Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015927","name":"Evans Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2026,7,16]]},"abstract":"<jats:p>\n                    Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e\/sQTL) analyses in six tissues and cell types, including whole blood (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 6454) and lung (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 1291). We detected tens of thousands of secondary cis-e\/sQTLs, showing that secondary cis-e\/sQTL discovery remains unsaturated. We fine-mapped UK Biobank\u2013derived genome-wide association study (GWAS) signals from 164 traits and identified e\/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e\/sQTLs. Our results suggest that even larger e\/sQTL analyses will uncover additional secondary e\/sQTLs, further benefiting GWAS interpretation.\n                  <\/jats:p>","DOI":"10.1126\/science.adx2989","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:03:38Z","timestamp":1784225018000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed"],"prefix":"10.1126","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-1106","authenticated-orcid":true,"given":"Peter","family":"Orchard","sequence":"first","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Blackwell","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA."},{"name":"Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3226-4727","authenticated-orcid":true,"given":"Linda","family":"Kachuri","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9920-4713","authenticated-orcid":true,"given":"Peter J.","family":"Castaldi","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4907-1657","authenticated-orcid":true,"given":"Michael H.","family":"Cho","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1550-2815","authenticated-orcid":true,"given":"Stephanie A.","family":"Christenson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, School of Medicine, University of California, San Francisco, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-2943","authenticated-orcid":true,"given":"Peter","family":"Durda","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-4334","authenticated-orcid":true,"given":"Craig P.","family":"Hersh","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."},{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-6191","authenticated-orcid":true,"given":"Scott","family":"Huntsman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San 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