{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:00:32Z","timestamp":1787032832654,"version":"build-2736575974"},"reference-count":84,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35-GM124836"],"award-info":[{"award-number":["R35-GM124836"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL139865"],"award-info":[{"award-number":["R01-HL139865"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL155915"],"award-info":[{"award-number":["R01-HL155915"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,28]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Causality between plasma triglyceride (TG) levels and atherosclerotic cardiovascular disease (ASCVD) risk remains controversial despite more than four decades of study and two recent landmark trials, STRENGTH, and REDUCE-IT. Further unclear is the association between TG levels and non-atherosclerotic diseases across organ systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Here, we conducted a phenome-wide, two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) regression to systematically infer the causal effects of plasma TG levels on 2600 disease traits in the European ancestry population of UK Biobank. For replication, we externally tested 221 nominally significant associations (p&lt;0.05) in an independent cohort from FinnGen. To account for potential horizontal pleiotropy and the influence of invalid instrumental variables, we performed sensitivity analyses using MR-Egger regression, weighted median estimator, and MR-PRESSO. Finally, we used multivariable MR (MVMR) controlling for correlated lipid fractions to distinguish the independent effect of plasma TG levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Our results identified seven disease traits reaching Bonferroni-corrected significance in both the discovery (p&lt;1.92 \u00d7 10\n                      <jats:sup>-5<\/jats:sup>\n                      ) and replication analyses (p&lt;2.26 \u00d7 10\n                      <jats:sup>-4<\/jats:sup>\n                      ), suggesting a causal relationship between plasma TG levels and ASCVDs, including coronary artery disease (OR 1.33, 95% CI 1.24\u20131.43, p=2.47 \u00d7 10\n                      <jats:sup>-13<\/jats:sup>\n                      ). We also identified 12 disease traits that were Bonferroni-significant in the discovery or replication analysis and at least nominally significant in the other analysis (p&lt;0.05), identifying plasma TG levels as a novel potential risk factor for nine non-ASCVD diseases, including uterine leiomyoma (OR 1.19, 95% CI 1.10\u20131.29, p=1.17 \u00d7 10\n                      <jats:sup>-5<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Taking a phenome-wide, two-sample MR approach, we identified causal associations between plasma TG levels and 19 disease traits across organ systems. Our findings suggest unrealized drug repurposing opportunities or adverse effects related to approved and emerging TG-lowering agents, as well as mechanistic insights for future studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>RD is supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) (R35-GM124836) and the National Heart, Lung, and Blood Institute of the NIH (R01-HL139865 and R01-HL155915).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.80560","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T06:15:44Z","timestamp":1680070544000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.80560","source":"Crossref","is-referenced-by-count":7,"title":["Phenome-wide Mendelian randomization study of plasma triglyceride levels and 2600 disease traits"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-3537","authenticated-orcid":true,"given":"Joshua K","family":"Park","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"publisher"}],"name":"Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai","place":["New York, United States"]},{"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai","place":["New York, United States"]},{"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Scientist Training Program, Icahn School of Medicine at Mount Sinai","place":["New York, United 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