{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:02Z","timestamp":1785434822378,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The criteria for distinguishing between association and causation in studies of genes and function are clarified. Genomic association scores alone cannot satisfy those criteria, which is why treatment of common diseases has not benefitted from the cures expected when the Human Genome Project was launched. Instead, causal understanding of function and disease requires detailed experimental data at the relevant levels of organization in the organism, from which quantitative physiological modelling then enables causal processes to be measured accurately. They can then be compared with association scores. An example shows how this process works in the heart and how that work led to the identification of a useful medication. Another major field of clinical importance is the nervous system, because nervous diseases were also expected to yield to genomics\u2010driven discoveries of genetic cures. That expectation also has not been fulfilled. It is now necessary to investigate causation at functional physiological levels of organization in order to develop strategies that can identify cures for multifactorial diseases.<\/jats:p>","DOI":"10.1113\/ep093664","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:13:37Z","timestamp":1782926017000},"page":"3546-3556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["How physiology solves the gene\u2010centric impasse"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-3694","authenticated-orcid":false,"given":"Denis","family":"Noble","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy &amp; Genetics University of Oxford  Oxford UK"},{"name":"Daegu\u2010Gyeongbuk Institute of Advanced Studies  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reine","family":"Bourret","sequence":"additional","affiliation":[{"name":"Independent researcher  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10358-1"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.7208\/chicago\/9780226826691.001.0001"},{"key":"e_1_2_17_4_1","unstructured":"Bridges E.(2026 January 08).NHS expenditure: Research briefing.House of Commons Library."},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1109\/10.284940"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/mec.12170"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907013410106"},{"key":"e_1_2_17_8_1","volume-title":"The astonishing hypothesis. The scientific search for the soul","author":"Crick F.","year":"1994"},{"key":"e_1_2_17_9_1","volume-title":"The extended phenotype","author":"Dawkins R.","year":"1982"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aed1656"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464160-00003"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adt2760"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/003591576505800503"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1150021"},{"issue":"1","key":"e_1_2_17_15_1","article-title":"Performance of polygenic risk scores in screening, prediction, and risk stratification: Secondary analysis of data in the polygenic score catalog","volume":"2","author":"Hingorani A. D.","year":"2023","journal-title":"British Medical Journal Medicine"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaf942"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1952.sp004764"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17951"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnetp.2021.711778"},{"key":"e_1_2_17_20_1","first-page":"96","volume-title":"The possible and the actual","author":"Jacob F.","year":"1982"},{"key":"e_1_2_17_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(61)80072-7"},{"key":"e_1_2_17_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbad023"},{"key":"e_1_2_17_23_1","volume-title":"The molecular vision of life: Caltech, the Rockefeller Foundation, and the rise of the new biology","author":"Kay L. E.","year":"1993"},{"key":"e_1_2_17_24_1","doi-asserted-by":"publisher","DOI":"10.1515\/9781503617575"},{"key":"e_1_2_17_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-026-02503-3"},{"key":"e_1_2_17_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/188495b0"},{"key":"e_1_2_17_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1962.sp006849"},{"key":"e_1_2_17_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780199295739.001.0001"},{"key":"e_1_2_17_29_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.2008.0086"},{"key":"e_1_2_17_30_1","doi-asserted-by":"publisher","DOI":"10.1017\/9781316584200.006"},{"key":"e_1_2_17_31_1","doi-asserted-by":"publisher","DOI":"10.1142\/q0532"},{"key":"e_1_2_17_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP287139"},{"key":"e_1_2_17_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP093268"},{"key":"e_1_2_17_34_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1992.0150"},{"key":"e_1_2_17_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolinnean\/blac049"},{"key":"e_1_2_17_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09866-3"},{"key":"e_1_2_17_37_1","volume-title":"What is life? The physical aspect of the living cell","author":"Schr\u00f6dinger E.","year":"1943"},{"key":"e_1_2_17_38_1","doi-asserted-by":"publisher","DOI":"10.31677\/2072-6724-2025-77-4-247-261"},{"key":"e_1_2_17_39_1","first-page":"016","article-title":"The linking of toxoplasmosis and schizophrenia","volume":"71","author":"Torrey E. F.","year":"2024","journal-title":"Folia Parasitologica"},{"key":"e_1_2_17_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-0736(95)80060-3"},{"key":"e_1_2_17_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/096914139400100401"},{"key":"e_1_2_17_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/096914139400100201"},{"key":"e_1_2_17_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/jms.6.3.117"},{"key":"e_1_2_17_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.319.7224.1562"},{"key":"e_1_2_17_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2010.378"},{"key":"e_1_2_17_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0418-5"},{"key":"e_1_2_17_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M116.060301"},{"key":"e_1_2_17_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2181665"},{"key":"e_1_2_17_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/171964b0"},{"key":"e_1_2_17_50_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.250200"},{"key":"e_1_2_17_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-804659-3.00001-4"},{"key":"e_1_2_17_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02133-w"},{"key":"e_1_2_17_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-64634-1"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP093664","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP093664","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP093664","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:44:51Z","timestamp":1785433491000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP093664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1113\/EP093664"],"URL":"https:\/\/doi.org\/10.1113\/ep093664","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"2026-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}