{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:55:03Z","timestamp":1788980103472,"version":"build-2803163510"},"reference-count":54,"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\">Smoking is a factor for hypertension. We aim to reveal novel plasma proteins mediating the relationship of smoking with hypertension and identify potential drug targets for hypertension on the basis of Mendelian randomization design.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Data for smoking were selected from the largest genome\u2010wide association study meta\u2010analysis performed by the Genome\u2010Wide Association Study and Sequencing Consortium of Alcohol and Nicotine Use. Data for plasma proteins were selected from the deCODE Health study and the UK Biobank Pharma Proteomics Project. Data for hypertension were extracted from the FinnGen Study. Moreover, proteome\u2010wide Mendelian randomization and colocalization analyses, 2\u2010step Mendelian randomization, and gene function and network prediction, as well as druggability assessment were performed. We finally identified 8 proteins (ANXA4 [annexin A4], DLK1 [protein delta homolog 1], KLB [\u03b2\u2010klotho], MMP8 [matrix metallopeptidase 8], PLAT [tissue\u2010type plasminogen activator], POSTN [periostin], SAT2 [thialysine N\u2010\u03b5\u2010acetyltransferase], and IFNLR1 [interferon \u03bb receptor 1]) mediating association of smoking with hypertension. PLAT and IFNLR1 were identified to be involved in the complement and coagulation cascades and the Janus kinase\/signal transducer and activator of transcription signaling pathway. ANXA4, KLB, MMP8, PLAT, and IFNLR1 had druggability. Moreover, IFNLR1 had strong evidence of genetic colocalization, because the posterior probability for H4 of IFNLR1 was 91.3%.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">This study identified the 8 proteins that mediate causal association between smoking and essential hypertension. Interferon \u03bb receptor agonist targeting IFNLR1 may open a new avenue for treating hypertension. Our discoveries provide new insights into protein pathogenesis of hypertension and to better guide hypertension prevention and treatment among smokers.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.036202","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T03:35:51Z","timestamp":1732764951000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of Novel Proteins Mediating Causal Association Between Smoking and Essential Hypertension: A Mendelian Randomization Study"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4443-7445","authenticated-orcid":false,"given":"Jikang","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition Peking University Shenzhen Hospital Shenzhen 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