{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:51:53Z","timestamp":1779195113005,"version":"3.51.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-54566-z","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T16:02:59Z","timestamp":1728403379000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel GWAS locus influences microvascular response to mental stress and predicts adverse cardiovascular events"],"prefix":"10.1038","volume":"14","author":[{"given":"Zakaria","family":"Almuwaqqat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Hammadah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman","family":"Alkhoder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Raggi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit J.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Douglas","family":"Bremner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viola","family":"Vaccarino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan V.","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arshed A.","family":"Quyyumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"54566_CR1","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1016\/j.jacc.2007.12.024","volume":"51","author":"JE Dimsdale","year":"2008","unstructured":"Dimsdale, J. E. Psychological stress and cardiovascular disease. J. Am. Coll. Cardiol. 51, 1237\u20131246 (2008).","journal-title":"J. Am. Coll. Cardiol."},{"key":"54566_CR2","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/nrcardio.2012.45","volume":"9","author":"A Steptoe","year":"2012","unstructured":"Steptoe, A. & Kivim\u00e4ki, M. Stress and cardiovascular disease. Nat. Rev. Cardiol. 9, 360 (2012).","journal-title":"Nat. Rev. Cardiol."},{"key":"54566_CR3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.neubiorev.2008.04.010","volume":"33","author":"A Steptoe","year":"2009","unstructured":"Steptoe, A. & Brydon, L. Emotional triggering of cardiac events. Neurosci. Biobehav. Rev. 33, 63\u201370 (2009).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"54566_CR4","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1136\/heartjnl-2014-307306","volume":"102","author":"SS Arri","year":"2016","unstructured":"Arri, S. S., Ryan, M., Redwood, S. R. & Marber, M. S. Mental stress-induced myocardial ischaemia. Heart 102, 472\u2013480 (2016).","journal-title":"Heart"},{"key":"54566_CR5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/clc.4960270307","volume":"27","author":"DA Goor","year":"2004","unstructured":"Goor, D. A. et al. Peripheral arterial tonometry: A diagnostic method for detection of myocardial ischemia induced during mental stress tests: A pilot study. Clinical Cardiology 27, 137\u2013141 (2004).","journal-title":"Clinical Cardiology"},{"key":"54566_CR6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1097\/PSY.0b013e318187c035","volume":"71","author":"MM Burg","year":"2009","unstructured":"Burg, M. M. et al. Non-invasive detection of risk for emotion provoked myocardial ischemia. Psychosomatic Med. 71, 14\u201320 (2009).","journal-title":"Psychosomatic Med."},{"key":"54566_CR7","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1002\/clc.20515","volume":"32","author":"M Hassan","year":"2009","unstructured":"Hassan, M. et al. Usefulness of peripheral arterial tonometry in the detection of mental stress-induced myocardial ischemia. Clin. Cardiol. 32, E1\u2013E6 (2009).","journal-title":"Clin. Cardiol."},{"key":"54566_CR8","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000321","volume":"2","author":"R Ramadan","year":"2013","unstructured":"Ramadan, R. et al. Myocardial ischemia during mental stress: Role of coronary artery disease burden and vasomotion. J. Am. Heart Assoc. 2, e000321 (2013).","journal-title":"J. Am. Heart Assoc."},{"key":"54566_CR9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.ijcard.2017.05.093","volume":"243","author":"M Hammadah","year":"2017","unstructured":"Hammadah, M. et al. Hemodynamic, catecholamine, vasomotor and vascular responses: Determinants of myocardial ischemia during mental stress. Int. J. Cardiol. 243, 47\u201353 (2017).","journal-title":"Int. J. Cardiol."},{"key":"54566_CR10","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1161\/CIRCRESAHA.119.315005","volume":"125","author":"JH Kim","year":"2019","unstructured":"Kim, J. H. et al. Peripheral vasoconstriction during mental stress and adverse cardiovascular outcomes in patients with coronary artery disease. Circ. Res. 125, 874\u2013883 (2019).","journal-title":"Circ. Res."},{"key":"54566_CR11","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.008532","volume":"7","author":"M Hammadah","year":"2018","unstructured":"Hammadah, M. et al. Coronary and peripheral vasomotor responses to mental stress. J. Am. Heart Assoc. 7, e008532 (2018).","journal-title":"J. Am. Heart Assoc."},{"key":"54566_CR12","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/0735-1097(94)90772-2","volume":"23","author":"JE Muller","year":"1994","unstructured":"Muller, J. E., Abela, G. S., Nesto, R. W. & Tofler, G. H. Triggers, acute risk factors and vulnerable plaques: The lexicon of a new frontier. J. Am. College Cardiol. 23, 809\u2013813 (1994).","journal-title":"J. Am. College Cardiol."},{"key":"54566_CR13","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1161\/CIRCULATIONAHA.105.596189","volume":"114","author":"H Tofler Geoffrey","year":"2006","unstructured":"Tofler Geoffrey, H. & Muller, J. E. Triggering of acute cardiovascular disease and potential preventive strategies. Circulation 114, 1863\u20131872 (2006).","journal-title":"Circulation"},{"key":"54566_CR14","doi-asserted-by":"publisher","first-page":"s5","DOI":"10.1016\/S0140-6736(99)90234-9","volume":"353","author":"V Fuster","year":"1999","unstructured":"Fuster, V., Fayad, Z. A. & Badimon, J. J. J. T. L. Acute coronary syndromes: Biology. Lancet 353, s5\u2013s9 (1999).","journal-title":"Lancet"},{"key":"54566_CR15","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1056\/NEJM197812072992303","volume":"299","author":"A Maseri","year":"1978","unstructured":"Maseri, A. et al. Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of \u201cpreinfarction\u201d angina. New England J. Med. 299, 1271\u20137 (1978).","journal-title":"New England J. Med."},{"key":"54566_CR16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.amjcard.2014.04.022","volume":"114","author":"J Wei","year":"2014","unstructured":"Wei, J. et al. Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac events in patients with coronary artery disease. Am. J. Cardiol. 114, 187\u2013192 (2014).","journal-title":"Am. J. Cardiol."},{"key":"54566_CR17","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/nrcardio.2012.45","volume":"9","author":"A Steptoe","year":"2012","unstructured":"Steptoe, A. & Kivimaki, M. Stress and cardiovascular disease. Nat. Rev. Cardiol. 9, 360\u2013370 (2012).","journal-title":"Nat. Rev. Cardiol."},{"key":"54566_CR18","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000321","volume":"2","author":"R Ramadan","year":"2013","unstructured":"Ramadan, R. et al. Myocardial ischemia during mental stress: Role of coronary artery disease burden and vasomotion. J. Am. Heart Assoc. 2, e000321 (2013).","journal-title":"J. Am. Heart Assoc."},{"key":"54566_CR19","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1097\/PSY.0000000000000442","volume":"79","author":"M Hammadah","year":"2017","unstructured":"Hammadah, M. et al. Al the mental stress ischemia prognosis study: Objectives, study design, and prevalence of inducible ischemia. Psychosom Med. 79, 311\u2013317 (2017).","journal-title":"Psychosom Med."},{"key":"54566_CR20","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1161\/CIRCULATIONAHA.117.030849","volume":"137","author":"V Vaccarino","year":"2018","unstructured":"Vaccarino, V. et al. Mental stress-induced-myocardial ischemia in young patients with recent myocardial infarction: Sex differences and mechanisms. Circulation 137, 794\u2013805 (2018).","journal-title":"Circulation"},{"key":"54566_CR21","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1093\/eurheartj\/ehs184","volume":"33","author":"K Thygesen","year":"2012","unstructured":"Thygesen, K. et al. Third universal definition of myocardial infarction. Eur. Heart J. 33, 2551\u20132567 (2012).","journal-title":"Eur. Heart J."},{"issue":"9","key":"54566_CR22","doi-asserted-by":"publisher","first-page":"e003630","DOI":"10.1161\/JAHA.116.003630","volume":"5","author":"V Vaccarino","year":"2016","unstructured":"Vaccarino, V. et al. Sex differences in mental stress-induced myocardial ischemia in patients with coronary heart disease. J. Am. Heart Assoc. 5(9), e003630 (2016).","journal-title":"J. Am. Heart Assoc."},{"key":"54566_CR23","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1001\/archinte.168.7.763","volume":"168","author":"M Hassan","year":"2008","unstructured":"Hassan, M. et al. Association of beta1-adrenergic receptor genetic polymorphism with mental stress-induced myocardial ischemia in patients with coronary artery disease. Arch. Int. Med. 168, 763\u2013770 (2008).","journal-title":"Arch. Int. Med."},{"key":"54566_CR24","doi-asserted-by":"publisher","DOI":"10.4161\/cib.26839","volume":"6","author":"L Shi","year":"2013","unstructured":"Shi, L. Dock protein family in brain development and neurological disease. Commun. Integr. Biol. 6, e26839 (2013).","journal-title":"Commun. Integr. Biol."},{"key":"54566_CR25","doi-asserted-by":"publisher","first-page":"3976","DOI":"10.1074\/jbc.M111.303156","volume":"287","author":"H Kang","year":"2012","unstructured":"Kang, H. et al. Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins. J. Biol. Chem. 287, 3976\u20133986 (2012).","journal-title":"J. Biol. Chem."},{"key":"54566_CR26","doi-asserted-by":"publisher","first-page":"7286","DOI":"10.1038\/ncomms8286","volume":"6","author":"S Abraham","year":"2015","unstructured":"Abraham, S. et al. A Rac\/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis. Nat. Commun. 6, 7286 (2015).","journal-title":"Nat. Commun."},{"key":"54566_CR27","doi-asserted-by":"publisher","first-page":"577","DOI":"10.3389\/fncel.2019.00577","volume":"13","author":"M Huang","year":"2019","unstructured":"Huang, M. et al. Two autism\/dyslexia linked variations of DOCK4 disrupt the gene function on Rac1\/Rap1 activation, neurite outgrowth, and synapse development. Front Cell Neurosci. 13, 577 (2019).","journal-title":"Front Cell Neurosci."},{"key":"54566_CR28","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/s41569-019-0210-5","volume":"16","author":"I Fernandez-Ruiz","year":"2019","unstructured":"Fernandez-Ruiz, I. Active LDL trafficking drives atherosclerosis. Nat. Rev. Cardiol. 16, 384 (2019).","journal-title":"Nat. Rev. Cardiol."},{"key":"54566_CR29","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1161\/01.CIR.92.8.2102","volume":"92","author":"JA Blumenthal","year":"1995","unstructured":"Blumenthal, J. A. et al. Mental stress-induced ischemia in the laboratory and ambulatory ischemia during daily life: Association and hemodynamic features. Circulation 92, 2102\u20132108 (1995).","journal-title":"Circulation"},{"key":"54566_CR30","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/0735-1097(94)90169-4","volume":"24","author":"JS Gottdiener","year":"1994","unstructured":"Gottdiener, J. S. et al. Induction of silent myocardial ischemia with mental stress testing: Relation to the triggers of ischemia during daily life activities to ischemic functional severity. J. Am. College Cardiol. 24, 1645\u20131651 (1994).","journal-title":"J. Am. College Cardiol."},{"key":"54566_CR31","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1038\/ng.3656","volume":"48","author":"S Das","year":"2016","unstructured":"Das, S. et al. Next-generation genotype imputation service and methods. Nat. Genet. 48, 1284\u20131287 (2016).","journal-title":"Nat. Genet."},{"key":"54566_CR32","first-page":"1423","volume":"32","author":"X Zhan","year":"2016","unstructured":"Zhan, X., Hu, Y., Li, B., Abecasis, G. R. & Liu, D. J. RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data. Bioinformatics (Oxford, England) 32, 1423\u20131426 (2016).","journal-title":"Bioinformatics (Oxford, England)"},{"key":"54566_CR33","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer, C. J., Li, Y. & Abecasis, G. R. METAL: Fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190\u20132191 (2010).","journal-title":"Bioinformatics"},{"key":"54566_CR34","first-page":"2336","volume":"26","author":"RJ Pruim","year":"2010","unstructured":"Pruim, R. J. et al. LocusZoom: Regional visualization of genome-wide association scan results. Bioinformatics (Oxford, England) 26, 2336\u20132337 (2010).","journal-title":"Bioinformatics (Oxford, England)"},{"key":"54566_CR35","doi-asserted-by":"publisher","first-page":"2662","DOI":"10.1161\/CIRCULATIONAHA.115.020723","volume":"133","author":"SD Solomon","year":"2016","unstructured":"Solomon, S. D. & Pfeffer, M. A. The future of clinical trials in cardiovascular medicine. Circulation 133, 2662\u20132670 (2016).","journal-title":"Circulation"},{"key":"54566_CR36","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/jrsm.1384","volume":"11","author":"VMT de Jong","year":"2020","unstructured":"de Jong, V. M. T. et al. Individual participant data meta-analysis of intervention studies with time-to-event outcomes: A review of the methodology and an applied example. Res. Synth. Methods 11, 148\u2013168 (2020).","journal-title":"Res. Synth. Methods"},{"key":"54566_CR37","doi-asserted-by":"crossref","unstructured":"Therneau, T. M., Grambsch, P. M. The Cox Model, in Modeling Survival Data: Extending the Cox Model. Statistics for Biology and Health. Springer, New York, NY. (2000).","DOI":"10.1007\/978-1-4757-3294-8"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54566-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54566-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54566-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T16:08:44Z","timestamp":1728403724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-54566-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["54566"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-54566-z","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]},"assertion":[{"value":"31 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2024","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":"23479"}}