{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:03:24Z","timestamp":1780369404763,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"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":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Chronotype describes an individual's day or night preference and is thought to exert health effects through circadian timing, yet continuous circadian measures related to chronotype have never been examined in large human cohorts. We sought to quantify wearable\u2010derived heart rate phase (HRP) as an indicator of chronotype\u2010relevant circadian shifts and determine its associations with human disease.\nHeart rate was aggregated over 5\u00a0min intervals in\n                      <jats:italic>All of Us<\/jats:italic>\n                      participants with wearable data and fit to a sine curve with 24\u00a0h period to determine HRP. Associations between HRP and circadian genomic variants were determined by linear regression. A phenome\u2010wide association study (PheWAS) was performed by multiple logistic regression. One\u2010sample Mendelian randomization (MR) was performed by two\u2010stage residual inclusion.\nAverage HRP was 9.48\u00a0\u00b1\u00a01.57\u00a0h (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a015,960). PheWAS identified phenome\u2010wide associations of later HRP with addiction, mood, sleep and metabolic disorders, while certain conditions of pregnancy were associated with earlier HRP. In focused analyses of type 2 diabetes mellitus (T2DM), later HRP was associated with increased T2DM risk [odds ratio (OR) 1.09 [1.06,1.13],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a01.58\u00a0\u00d7\u00a010\n                      <jats:sup>\u22127<\/jats:sup>\n                      ). The morningness genomic variant rs1144566(T) was associated with earlier HRP (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a01.38\u00a0\u00d7\u00a010\n                      <jats:sup>\u22127<\/jats:sup>\n                      ) and decreased risk of T2DM (OR 0.69 [0.55,0.88],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a02.67\u00a0\u00d7\u00a010\n                      <jats:sup>\u22123<\/jats:sup>\n                      ). MR analysis suggested a causal effect of rs1144566 on T2DM risk through HRP (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a02.70\u00a0\u00d7\u00a010\n                      <jats:sup>\u22123<\/jats:sup>\n                      ).\nWe introduce the use of a quantitative longitudinal circadian metric, HRP. We combine HRP with phenomics, genomics and electronic health records data to provide evidence for a relationship between circadian shifts and disease. HRP may hold value in the management and surveillance of human health.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70471-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Chronotype is a genetically influenced innate preference for the timing of daily activity and is believed to affect health outcomes through shifts in circadian rhythms.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Measurement of chronotype\u2010relevant circadian changes may be possible through wearable technology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We show that the timing of daily heart rate rhythms, which we call heart rate phase (HRP), is associated with chronotype\u2010relevant genetic and demographic factors.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We report associations of HRP with addiction, mood, sleep and metabolism disorders as well as certain pregnancy conditions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We show that HRP is associated with type 2 diabetes mellitus (T2DM) risk and that a morning genetic chronotype variant may causally influence T2DM risk through HRP.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290337","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:01:02Z","timestamp":1773720062000},"page":"3282-3296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Heart rate phase is an indicator of chronotype\u2010relevant circadian shifts associated with human disease: an\n                    <i>All of Us<\/i>\n                    Research Program analysis"],"prefix":"10.1113","volume":"604","author":[{"given":"Zachary M.","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya P.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella M.","family":"Levitsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen A.","family":"McClung","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Department of Psychiatry University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7465-0581","authenticated-orcid":false,"given":"Seyed Mehdi","family":"Nouraie","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center  Pittsburgh Pennsylvania USA"},{"name":"Division of Pulmonary Allergy, Critical Care Medicine, and Sleep Medicine Department of Medicine University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center  Pittsburgh Pennsylvania 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