{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T05:39:32Z","timestamp":1757309972969,"version":"3.41.2"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Although utility of composite trait\u2010specific polygenic risk score (multi\u2010trait PRS) has been examined among European ancestries, few studies investigated among East Asians and incorporated modifiable risk factors. We examined the associations of multi\u2010trait PRS for cardiometabolic factors with cardiovascular disease mortality by integrating nongenetic determinants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">A total of 14\u2009086 Japanese participants (mean age, 55\u00b19; 55.8% women) of the J\u2010MICC (Japan Multi\u2010Institutional Collaborative Cohort) study were analyzed in this study. We calculated 6 PRSs for cardiometabolic traits (systolic blood pressure, body mass index, triglycerides, low\u2010density lipoprotein cholesterol, estimated glomerular filtration rate, and hemoglobin A1c). Based on these PRSs, we developed multi\u2010trait PRS and considered as a primary exposure. Three nongenetic factors (smoking, alcohol drinking, and educational attainment) from the self\u2010reported questionnaire were also examined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">During a median 12.1\u2010year follow\u2010up period, a total of 472 all\u2010cause and 79 cardiovascular disease mortality cases were documented. Compared with 0% to 90% of multi\u2010trait PRSs, an adjusted hazard ratio (HR) among the top 10% of multi\u2010trait PRSs was 1.32 (95% CI, 1.00\u20131.73) for all\u2010cause death and 2.63 (95% CI, 1.48\u20134.67) for cardiovascular disease death. Incorporation of educational attainment with multi\u2010trait PRSs showed null associations in those who went beyond high school (HR, 2.07 [95% CI, 0.44\u20139.66]) even in the top 10% of multi\u2010trait PRS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our analysis combining both genetic and nongenetic determinants highlighted that lifestyle factors and educational attainment can slightly reduce an individual's composite genetic risk for cardiovascular disease death.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.038572","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T10:36:28Z","timestamp":1741862188000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Multi\u2010Trait Polygenic Risk Score, Nongenetic Determinants, and Cardiovascular Disease Death: A Cohort Study of 14\u2009086 Japanese Individuals"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1730-2059","authenticated-orcid":false,"given":"Ryosuke","family":"Fujii","sequence":"first","affiliation":[{"name":"Fujita Health University School of Medical Sciences","place":["Toyoake, Japan"]},{"name":"Nagoya University Graduate School of Medicine","place":["Nagoya, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1196-146X","authenticated-orcid":false,"given":"Mako","family":"Nagayoshi","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine","place":["Nagoya, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-4837","authenticated-orcid":false,"given":"Masahiro","family":"Nakatochi","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine","place":["Nagoya, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-3649","authenticated-orcid":false,"given":"Shuntaro","family":"Sato","sequence":"additional","affiliation":[{"name":"Nagasaki University Hospital","place":["Nagasaki, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8145-3949","authenticated-orcid":false,"given":"Yoshiki","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Fujita Health University School of Medical Sciences","place":["Toyoake, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-9558","authenticated-orcid":false,"given":"Koji","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Fujita Health University School of Medical Sciences","place":["Toyoake, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6677-6341","authenticated-orcid":false,"given":"Hiroaki","family":"Ikezaki","sequence":"additional","affiliation":[{"name":"Kyushu University","place":["Fukuoka, Japan"]},{"name":"Kyushu University Hospital","place":["Fukuoka, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2320-7234","authenticated-orcid":false,"given":"Yuichiro","family":"Nishida","sequence":"additional","affiliation":[{"name":"Saga University","place":["Saga, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8390-0299","authenticated-orcid":false,"given":"Yoko","family":"Kubo","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine","place":["Nagoya, 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