{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T08:10:34Z","timestamp":1781424634580,"version":"3.54.1"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Digit. Med."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Circadian rhythms are crucial for regulating physiological and behavioral processes. Pineal hormone melatonin is often used to measure circadian amplitude but its collection is costly and time-consuming. Wearable activity data are promising alternative, but the most commonly used measure, relative amplitude, is subject to behavioral masking. In this study, we firstly derive a feature named <jats:bold>c<\/jats:bold>ircadian <jats:bold>a<\/jats:bold>ctivity <jats:bold>r<\/jats:bold>hythm <jats:bold>e<\/jats:bold>nergy (CARE) to better characterize circadian amplitude and validate CARE by correlating it with melatonin amplitude (Pearson\u2019s <jats:italic>r<\/jats:italic>\u2009=\u20090.46, <jats:italic>P<\/jats:italic>\u2009=\u20090.007) among 33 healthy participants. Then we investigate its association with cognitive functions in an adolescent dataset (Chinese SCHEDULE-A, n\u2009=\u20091703) and an adult dataset (UK Biobank, <jats:italic>n<\/jats:italic>\u2009=\u200992,202), and find that CARE is significantly associated with Global Executive Composite (<jats:italic>\u03b2<\/jats:italic>\u2009=\u200930.86, <jats:italic>P<\/jats:italic>\u2009=\u20090.016) in adolescents, and reasoning ability, short-term memory, and prospective memory (<jats:italic>OR<\/jats:italic>\u2009=\u20090.01, 3.42, and 11.47 respectively, all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) in adults. Finally, we identify one genetic locus with 126 CARE-associated SNPs using the genome-wide association study, of which 109 variants are used as instrumental variables in the Mendelian Randomization analysis, and the results show a significant causal effect of CARE on reasoning ability, short-term memory, and prospective memory (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009-59.91, 7.94, and 16.85 respectively, all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). The present study suggests that CARE is an effective wearable-based metric of circadian amplitude with a strong genetic basis and clinical significance, and its adoption can facilitate future circadian studies and potential intervention strategies to improve circadian rhythms and cognitive functions.<\/jats:p>","DOI":"10.1038\/s41746-023-00865-0","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T07:02:22Z","timestamp":1689058942000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["CARE as a wearable derived feature linking circadian amplitude to human cognitive functions"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0871-3529","authenticated-orcid":false,"given":"Shuya","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3424-9659","authenticated-orcid":false,"given":"Qingmin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Gui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8347-0830","authenticated-orcid":false,"given":"Hui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-9607","authenticated-orcid":false,"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-1906","authenticated-orcid":false,"given":"Xiaolei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1972-9021","authenticated-orcid":false,"given":"Xinyue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0634-101X","authenticated-orcid":false,"given":"Fan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,11]]},"reference":[{"key":"865_CR1","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1113\/expphysiol.2012.071118","volume":"99","author":"RG Foster","year":"2014","unstructured":"Foster, R. G. & Kreitzman, L. The rhythms of life: what your body clock means to you! Exp. Physiol. 99, 599\u2013606 (2014).","journal-title":"Exp. Physiol."},{"key":"865_CR2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1111\/joim.12347","volume":"277","author":"C Dibner","year":"2015","unstructured":"Dibner, C. & Schibler, U. Circadian timing of metabolism in animal models and humans. J. Intern. Med. 277, 513\u2013527 (2015).","journal-title":"J. Intern. Med."},{"key":"865_CR3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/joim.12924","volume":"286","author":"P Zimmet","year":"2019","unstructured":"Zimmet, P. et al. The circadian syndrome: is the metabolic syndrome and much more! J. Intern. Med. 286, 181\u2013191 (2019).","journal-title":"J. Intern. Med."},{"key":"865_CR4","doi-asserted-by":"publisher","first-page":"883","DOI":"10.3390\/cells8080883","volume":"8","author":"D Chowdhury","year":"2019","unstructured":"Chowdhury, D. et al. Understanding quantitative circadian regulations are crucial towards advancing chronotherapy. Cells 8, 883 (2019).","journal-title":"Cells"},{"key":"865_CR5","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1080\/23328940.2020.1743605","volume":"7","author":"R Refinetti","year":"2020","unstructured":"Refinetti, R. Circadian rhythmicity of body temperature and metabolism. Temperature 7, 321\u2013362 (2020).","journal-title":"Temperature"},{"key":"865_CR6","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1146\/annurev-physiol-021909-135919","volume":"72","author":"DK Welsh","year":"2010","unstructured":"Welsh, D. K., Takahashi, J. S. & Kay, S. A. Suprachiasmatic nucleus: cell autonomy and network properties. Annu. Rev. Physiol. 72, 551\u2013577 (2010).","journal-title":"Annu. Rev. Physiol."},{"key":"865_CR7","doi-asserted-by":"crossref","unstructured":"Buhr, E. D. & Takahashi J. S. Molecular components of the Mammalian circadian clock. Handb. Exp. Pharmacol. 3\u201327 (2013).","DOI":"10.1007\/978-3-642-25950-0_1"},{"key":"865_CR8","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1101\/sqb.2015.80.027490","volume":"80","author":"U Schibler","year":"2015","unstructured":"Schibler, U. et al. Clock-talk: interactions between central and peripheral circadian oscillators in mammals. Cold Spring Harb. Symp. Quant. Biol. 80, 223\u2013232 (2015).","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"865_CR9","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S1474-4422(18)30461-7","volume":"18","author":"Y Leng","year":"2019","unstructured":"Leng, Y. et al. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 18, 307\u2013318 (2019).","journal-title":"Lancet Neurol."},{"key":"865_CR10","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1093\/biostatistics\/kxt020","volume":"14","author":"MJ Costa","year":"2013","unstructured":"Costa, M. J. et al. Inference on periodicity of circadian time series. Biostatistics 14, 792\u2013806 (2013).","journal-title":"Biostatistics"},{"key":"865_CR11","doi-asserted-by":"publisher","first-page":"e18403","DOI":"10.2196\/18403","volume":"23","author":"X Li","year":"2021","unstructured":"Li, X. et al. Circadian rhythm analysis using wearable device data: novel penalized machine learning approach. J. Med. Internet Res. 23, e18403 (2021).","journal-title":"J. Med. Internet Res."},{"key":"865_CR12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1177\/0748730410391619","volume":"26","author":"V Kolodyazhniy","year":"2011","unstructured":"Kolodyazhniy, V. et al. Estimation of human circadian phase via a multi-channel ambulatory monitoring system and a multiple regression model. J. Biol. Rhythms 26, 55\u201367 (2011).","journal-title":"J. Biol. Rhythms"},{"key":"865_CR13","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.3109\/07420528.2012.700669","volume":"29","author":"V Kolodyazhniy","year":"2012","unstructured":"Kolodyazhniy, V. et al. An improved method for estimating human circadian phase derived from multichannel ambulatory monitoring and artificial neural networks. Chronobiol. Int. 29, 1078\u20131097 (2012).","journal-title":"Chronobiol. Int."},{"key":"865_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47311-4","volume":"9","author":"JE Stone","year":"2019","unstructured":"Stone, J. E. et al. Generalizability of a neural network model for circadian phase prediction in real-world conditions. Sci. Rep. 9, 11001 (2019).","journal-title":"Sci. Rep."},{"key":"865_CR15","doi-asserted-by":"crossref","unstructured":"Brown, L. S. et al. A classification approach to estimating human circadian phase under circadian alignment from actigraphy and photometry data. J. Pineal Res. 71, e12745 (2021).","DOI":"10.1111\/jpi.12745"},{"key":"865_CR16","doi-asserted-by":"crossref","unstructured":"Cheng, P. et al. Predicting circadian misalignment with wearable technology: validation of wrist-worn actigraphy and photometry in night shift workers. Sleep 44, zsaa180 (2021).","DOI":"10.1093\/sleep\/zsaa180"},{"key":"865_CR17","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.coisb.2020.07.011","volume":"22","author":"JE Stone","year":"2020","unstructured":"Stone, J. E. et al. Computational approaches for individual circadian phase prediction in field settings. Curr. Opin. Syst. Biol. 22, 39\u201351 (2020).","journal-title":"Curr. Opin. Syst. Biol."},{"key":"865_CR18","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1177\/0748730420940483","volume":"35","author":"DJ Dijk","year":"2020","unstructured":"Dijk, D. J. & Duffy, J. F. Novel approaches for assessing circadian rhythmicity in humans: a review. J. Biol. Rhythms 35, 421\u2013438 (2020).","journal-title":"J. Biol. Rhythms"},{"key":"865_CR19","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/350059a0","volume":"350","author":"ME Jewett","year":"1991","unstructured":"Jewett, M. E., Kronauer, R. E. & Czeisler, C. A. Light-induced suppression of endogenous circadian amplitude in humans. Nature 350, 59\u201362 (1991).","journal-title":"Nature"},{"key":"865_CR20","doi-asserted-by":"publisher","first-page":"e30037","DOI":"10.1371\/journal.pone.0030037","volume":"7","author":"D-J Dijk","year":"2012","unstructured":"Dijk, D.-J. et al. Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans. PLoS ONE 7, e30037 (2012).","journal-title":"PLoS ONE"},{"key":"865_CR21","doi-asserted-by":"publisher","first-page":"66","DOI":"10.5664\/jcsm.27083","volume":"04","author":"S Benloucif","year":"2008","unstructured":"Benloucif, S. et al. Measuring melatonin in humans. J. Clin. Sleep. Med. 04, 66\u201369 (2008).","journal-title":"J. Clin. Sleep. Med."},{"key":"865_CR22","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/0006-3223(90)90523-5","volume":"27","author":"W Witting","year":"1990","unstructured":"Witting, W. et al. Alterations in the circadian rest-activity rhythm in aging and Alzheimer\u2019s disease. Biol. Psychiatry 27, 563\u2013572 (1990).","journal-title":"Biol. Psychiatry"},{"key":"865_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/1740-3391-11-5","volume":"11","author":"TL Leise","year":"2013","unstructured":"Leise, T. L. Wavelet analysis of circadian and ultradian behavioral rhythms. J. Circadian Rhythms 11, 5 (2013).","journal-title":"J. Circadian Rhythms"},{"key":"865_CR24","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1093\/sleep\/26.3.342","volume":"26","author":"S Ancoli-Israel","year":"2003","unstructured":"Ancoli-Israel, S. et al. The role of actigraphy in the study of sleep and circadian rhythms. Sleep 26, 342\u2013392 (2003).","journal-title":"Sleep"},{"key":"865_CR25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.freeradbiomed.2017.11.003","volume":"119","author":"I Heyde","year":"2018","unstructured":"Heyde, I., Kiehn, J.-T. & Oster, H. Mutual influence of sleep and circadian clocks on physiology and cognition. Free Radic. Biol. Med. 119, 8\u201316 (2018).","journal-title":"Free Radic. Biol. Med."},{"key":"865_CR26","doi-asserted-by":"publisher","first-page":"114438","DOI":"10.1016\/j.bcp.2021.114438","volume":"191","author":"J Taillard","year":"2021","unstructured":"Taillard, J. et al. Sleep timing, chronotype and social jetlag: Impact on cognitive abilities and psychiatric disorders. Biochem. Pharmacol. 191, 114438 (2021).","journal-title":"Biochem. Pharmacol."},{"key":"865_CR27","doi-asserted-by":"publisher","first-page":"667","DOI":"10.2174\/1567205018666211124104710","volume":"18","author":"M Wang","year":"2021","unstructured":"Wang, M. et al. Altered biological rhythm and Alzheimer\u2019s disease: a bidirectional relationship. Curr. Alzheimer Res. 18, 667\u2013675 (2021).","journal-title":"Curr. Alzheimer Res."},{"key":"865_CR28","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1002\/ana.22468","volume":"70","author":"GJ Tranah","year":"2011","unstructured":"Tranah, G. J. et al. Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women. Ann. Neurol. 70, 722\u2013732 (2011).","journal-title":"Ann. Neurol."},{"key":"865_CR29","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","volume":"62","author":"RC Kessler","year":"2005","unstructured":"Kessler, R. C. et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch. Gen. Psychiatry 62, 593\u2013602 (2005).","journal-title":"Arch. Gen. Psychiatry"},{"key":"865_CR30","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.yfrne.2012.04.003","volume":"33","author":"MH Hagenauer","year":"2012","unstructured":"Hagenauer, M. H. & Lee, T. M. The neuroendocrine control of the circadian system: adolescent chronotype. Front. Neuroendocrinol. 33, 211\u2013229 (2012).","journal-title":"Front. Neuroendocrinol."},{"key":"865_CR31","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/S2215-0366(18)30172-X","volume":"5","author":"A Doherty","year":"2018","unstructured":"Doherty, A. Circadian rhythms and mental health: wearable sensing at scale. Lancet Psychiatry 5, 457\u2013458 (2018).","journal-title":"Lancet Psychiatry"},{"key":"865_CR32","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S2215-0366(18)30139-1","volume":"5","author":"LM Lyall","year":"2018","unstructured":"Lyall, L. M. et al. Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: a cross-sectional study of 91\u2008105 participants from the UK Biobank. Lancet Psychiatry 5, 507\u2013514 (2018).","journal-title":"Lancet Psychiatry"},{"key":"865_CR33","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.ebiom.2018.08.004","volume":"35","author":"A Ferguson","year":"2018","unstructured":"Ferguson, A. et al. Genome-wide association study of circadian rhythmicity in 71,500 UK Biobank participants and polygenic association with mood instability. EBioMedicine 35, 279\u2013287 (2018).","journal-title":"EBioMedicine"},{"key":"865_CR34","doi-asserted-by":"crossref","unstructured":"Hassani, H. Singular spectrum analysis: methodology and comparison. J. Data Sci. 5, 239\u2013257 (2007).","DOI":"10.6339\/JDS.2007.05(2).396"},{"key":"865_CR35","doi-asserted-by":"crossref","unstructured":"Hassani, H., Mahmoudvand, R., Zokaei, M. & Ghodsi, M. On the separability between signal and noise in singular spectrum analysis. Fluct. Noise Lett. 11, 1250014 (2012).","DOI":"10.1142\/S0219477512500149"},{"key":"865_CR36","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1177\/0748730412468693","volume":"28","author":"TL Leise","year":"2013","unstructured":"Leise, T. L. et al. Wavelet meets actogram. J. Biol. Rhythms 28, 62\u201368 (2013).","journal-title":"J. Biol. Rhythms"},{"key":"865_CR37","doi-asserted-by":"crossref","unstructured":"Gioia, G. A., Isquith P. K. & Roth R. M. in Encyclopedia of Clinical Neuropsychology (eds Kreutzer, J. S., DeLuca, J. & Caplan, B.) 532\u2013538 (Springer International Publishing, 2018).","DOI":"10.1007\/978-3-319-57111-9_1881"},{"key":"865_CR38","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.biopsych.2022.06.034","volume":"93","author":"AS Hatoum","year":"2023","unstructured":"Hatoum, A. S. et al. Genome-wide association study shows that executive functioning is influenced by GABAergic processes and is a neurocognitive genetic correlate of psychiatric disorders. Biol. Psychiatry 93, 59\u201370 (2023).","journal-title":"Biol. Psychiatry"},{"key":"865_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13585-5","volume":"10","author":"WD Hill","year":"2019","unstructured":"Hill, W. D. et al. Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income. Nat. Commun. 10, 5741 (2019).","journal-title":"Nat. Commun."},{"key":"865_CR40","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/mp.2016.45","volume":"21","author":"G Davies","year":"2016","unstructured":"Davies, G. et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112\u2009151). Mol. Psychiatry 21, 758\u2013767 (2016).","journal-title":"Mol. Psychiatry"},{"key":"865_CR41","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","volume":"37","author":"S Burgess","year":"2013","unstructured":"Burgess, S., Butterworth, A. & Thompson, S. G. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet. Epidemiol. 37, 658\u2013665 (2013).","journal-title":"Genet. Epidemiol."},{"key":"865_CR42","doi-asserted-by":"publisher","first-page":"e0222362","DOI":"10.1371\/journal.pone.0222362","volume":"14","author":"JMB Rees","year":"2019","unstructured":"Rees, J. M. B. et al. Robust methods in Mendelian randomization via penalization of heterogeneous causal estimates. PLoS ONE 14, e0222362 (2019).","journal-title":"PLoS ONE"},{"key":"865_CR43","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1093\/ije\/dyx102","volume":"46","author":"FP Hartwig","year":"2017","unstructured":"Hartwig, F. P., Davey Smith, G. & Bowden, J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int. J. Epidemiol. 46, 1985\u20131998 (2017).","journal-title":"Int. J. Epidemiol."},{"key":"865_CR44","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1016\/j.ajhg.2021.05.014","volume":"108","author":"H Xue","year":"2021","unstructured":"Xue, H., Shen, X. & Pan, W. Constrained maximum likelihood-based Mendelian randomization robust to both correlated and uncorrelated pleiotropic effects. Am. J. Hum. Genet .108, 1251\u20131269 (2021).","journal-title":"Am. J. Hum. Genet"},{"key":"865_CR45","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1038\/s41588-021-00892-1","volume":"53","author":"AR Barton","year":"2021","unstructured":"Barton, A. R. et al. Whole-exome imputation within UK Biobank powers rare coding variant association and fine-mapping analyses. Nat. Genet. 53, 1260\u20131269 (2021).","journal-title":"Nat. Genet."},{"key":"865_CR46","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/s42003-022-03607-2","volume":"5","author":"EO Adewuyi","year":"2022","unstructured":"Adewuyi, E. O. et al. A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer\u2019s disease and gastrointestinal tract disorders. Commun. Biol. 5, 691 (2022).","journal-title":"Commun. Biol."},{"key":"865_CR47","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1159\/000525411","volume":"81","author":"S Rao","year":"2022","unstructured":"Rao, S. et al. Genetic relationships between attention-deficit\/hyperactivity disorder, autism spectrum disorder, and intelligence. Neuropsychobiology 81, 484\u2013496 (2022).","journal-title":"Neuropsychobiology"},{"key":"865_CR48","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s41588-018-0333-3","volume":"51","author":"PR Jansen","year":"2019","unstructured":"Jansen, P. R. et al. Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. Nat. Genet. 51, 394\u2013403 (2019).","journal-title":"Nat. Genet."},{"key":"865_CR49","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.ajhg.2018.09.009","volume":"103","author":"S Ligthart","year":"2018","unstructured":"Ligthart, S. et al. Genome analyses of >200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders. Am. J. Hum. Genet. 103, 691\u2013706 (2018).","journal-title":"Am. J. Hum. Genet."},{"key":"865_CR50","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s42003-020-0921-5","volume":"3","author":"GR Oskarsson","year":"2020","unstructured":"Oskarsson, G. R. et al. Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis. Commun. Biol. 3, 189 (2020).","journal-title":"Commun. Biol."},{"key":"865_CR51","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.jaci.2019.09.035","volume":"145","author":"Z Zhu","year":"2020","unstructured":"Zhu, Z. et al. Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank. J. Allergy Clin. Immunol. 145, 537\u2013549 (2020).","journal-title":"J. Allergy Clin. Immunol."},{"key":"865_CR52","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1038\/s41588-022-01165-1","volume":"54","author":"Z Wang","year":"2022","unstructured":"Wang, Z. et al. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention. Nat. Genet. 54, 1332\u20131344 (2022).","journal-title":"Nat. Genet."},{"key":"865_CR53","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1038\/s41588-018-0152-6","volume":"50","author":"JE Savage","year":"2018","unstructured":"Savage, J. E. et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat. Genet. 50, 912\u2013919 (2018).","journal-title":"Nat. Genet."},{"key":"865_CR54","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/hmg\/ddy327","volume":"28","author":"SL Pulit","year":"2019","unstructured":"Pulit, S. L. et al. Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry. Hum. Mol. Genet. 28, 166\u2013174 (2019).","journal-title":"Hum. Mol. Genet."},{"key":"865_CR55","doi-asserted-by":"publisher","first-page":"e3055","DOI":"10.1371\/journal.pone.0003055","volume":"3","author":"HJ Burgess","year":"2008","unstructured":"Burgess, H. J. & Fogg, L. F. Individual differences in the amount and timing of salivary melatonin secretion. PLoS ONE 3, e3055 (2008).","journal-title":"PLoS ONE"},{"key":"865_CR56","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1034\/j.1600-079X.2003.01897.x","volume":"34","author":"J-N Zhou","year":"2003","unstructured":"Zhou, J.-N. et al. Alterations in the circadian rhythm of salivary melatonin begin during middle-age. J. Pineal Res. 34, 11\u201316 (2003).","journal-title":"J. Pineal Res."},{"key":"865_CR57","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.pneurobio.2010.12.004","volume":"93","author":"R Hardeland","year":"2011","unstructured":"Hardeland, R. et al. Melatonin\u2014a pleiotropic, orchestrating regulator molecule. Prog. Neurobiol. 93, 350\u2013384 (2011).","journal-title":"Prog. Neurobiol."},{"key":"865_CR58","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1177\/0748730410374943","volume":"25","author":"SW Cain","year":"2010","unstructured":"Cain, S. W. et al. Sex differences in phase angle of entrainment and melatonin amplitude in humans. J. Biol. Rhythms 25, 288\u2013296 (2010).","journal-title":"J. Biol. Rhythms"},{"key":"865_CR59","doi-asserted-by":"publisher","first-page":"e1009089","DOI":"10.1371\/journal.pgen.1009089","volume":"16","author":"X Li","year":"2020","unstructured":"Li, X. & Zhao, H. Automated feature extraction from population wearable device data identified novel loci associated with sleep and circadian rhythms. PLoS Genet. 16, e1009089 (2020).","journal-title":"PLoS Genet."},{"key":"865_CR60","doi-asserted-by":"publisher","first-page":"338764","DOI":"10.1016\/j.aca.2021.338764","volume":"1176","author":"W Jin","year":"2021","unstructured":"Jin, W. et al. High-throughput quantitation of trace level melatonin in human milk by on-line enrichment liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta 1176, 338764 (2021).","journal-title":"Anal. Chim. Acta"},{"key":"865_CR61","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.sleep.2007.03.012","volume":"8","author":"EJW Van Someren","year":"2007","unstructured":"Van Someren, E. J. W. & Nagtegaal, E. Improving melatonin circadian phase estimates. Sleep Med. 8, 590\u2013601 (2007).","journal-title":"Sleep Med."},{"key":"865_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s13034-022-00468-9","volume":"16","author":"Q Lin","year":"2022","unstructured":"Lin, Q. et al. Weight spectrum and executive function in adolescents: the moderating role of negative emotions. Child Adolesc. Psychiatry Ment. Health 16, 34 (2022).","journal-title":"Child Adolesc. Psychiatry Ment. Health"},{"key":"865_CR63","first-page":"277","volume":"39","author":"Y Qian","year":"2007","unstructured":"Qian, Y. & Wang, Y. F. [Reliability and validity of behavior rating scale of executive function parent form for school age children in China]. Beijing Da Xue Xue Bao Yi Xue Ban. 39, 277\u2013283 (2007).","journal-title":"Beijing Da Xue Xue Bao Yi Xue Ban."},{"key":"865_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).","journal-title":"Gigascience"},{"key":"865_CR65","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ng.3211","volume":"47","author":"BK Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan, B. K. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291\u2013295 (2015).","journal-title":"Nat. Genet."},{"key":"865_CR66","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1038\/ng.3954","volume":"49","author":"S Gazal","year":"2017","unstructured":"Gazal, S. et al. Linkage disequilibrium\u2013dependent architecture of human complex traits shows action of negative selection. Nat. Genet. 49, 1421\u20131427 (2017).","journal-title":"Nat. Genet."},{"key":"865_CR67","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1093\/ije\/dyx034","volume":"46","author":"OO Yavorska","year":"2017","unstructured":"Yavorska, O. O. & Burgess, S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int. J. Epidemiol. 46, 1734\u20131739 (2017).","journal-title":"Int. J. Epidemiol."},{"key":"865_CR68","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden, J. et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 40, 304\u2013314 (2016).","journal-title":"Genet. Epidemiol."},{"key":"865_CR69","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/jrsm.1346","volume":"10","author":"J Bowden","year":"2019","unstructured":"Bowden, J. & Holmes, M. V. Meta-analysis and Mendelian randomization: a review. Res. Synth. Methods 10, 486\u2013496 (2019).","journal-title":"Res. Synth. Methods"},{"key":"865_CR70","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/s41588-019-0345-7","volume":"51","author":"Y Hu","year":"2019","unstructured":"Hu, Y. et al. A statistical framework for cross-tissue transcriptome-wide association analysis. Nat. Genet. 51, 568\u2013576 (2019).","journal-title":"Nat. Genet."}],"container-title":["npj Digital Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41746-023-00865-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-023-00865-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-023-00865-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T08:05:03Z","timestamp":1689062703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41746-023-00865-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,11]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["865"],"URL":"https:\/\/doi.org\/10.1038\/s41746-023-00865-0","relation":{},"ISSN":["2398-6352"],"issn-type":[{"value":"2398-6352","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,11]]},"assertion":[{"value":"23 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"123"}}