{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T12:09:25Z","timestamp":1769083765738,"version":"3.49.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","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","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Drug Discov."],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is characterized by remodeling and narrowing of the pulmonary vasculature which results in elevations of pulmonary arterial pressures. Here, we conducted a genome-wide association study (GWAS) using the UK Biobank, analyzing the genomes of 493 individuals diagnosed with primary pulmonary hypertension, based on ICD-10 coding, compared to 24,650 age, sex, and ancestry-matched controls in a 1:50 case-control design. Genetic variants were analyzed by Plink\u2019s firth logistic regression and assessed for association with primary pulmonary hypertension. We identified three linked variants in the <jats:italic>PIM1<\/jats:italic> gene, which encodes a protooncogene that has been garnering interest as a potential therapeutic target for PAH, that were associated with PAH with genome wide significance, one (rs192449585) of which lies in the promoter region of the gene. We also identified 15 linked variants in the <jats:italic>LINC01491<\/jats:italic> gene. These results provide genetic evidence supporting the role of <jats:italic>PIM1<\/jats:italic> inhibitors as a potential therapeutic option for PAH.<\/jats:p>","DOI":"10.3389\/fddsv.2023.1127736","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T05:45:06Z","timestamp":1675835106000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of novel genetic variants, including PIM1 and LINC01491, with ICD-10 based diagnosis of pulmonary arterial hypertension in the UK Biobank cohort"],"prefix":"10.3389","volume":"3","author":[{"given":"Alex","family":"Pu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gautam","family":"Ramani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ju","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Perry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles C.","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0273217","DOI":"10.1371\/journal.pone.0273217","article-title":"Identifying genetic variants associated with the ICD10 (International Classification of Diseases10)-based diagnosis of cerebrovascular disease using a large-scale biomedical database","volume":"17","author":"Alkhalfan","year":"2022","journal-title":"PloS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0247287","DOI":"10.1371\/journal.pone.0247287","article-title":"Identification of novel genetic susceptibility loci for thoracic and abdominal aortic aneurysms via genome-wide association study using the UK Biobank Cohort","volume":"16","author":"Ashvetiya","year":"2021","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3390\/nu12010169","article-title":"Impact of nutrition on pulmonary arterial hypertension","volume":"12","author":"Callejo","year":"2020","journal-title":"Nutrients"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: Rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1038\/s41467-018-03672-4","article-title":"Identification of rare sequence variation underlying heritable pulmonary arterial hypertension","volume":"9","author":"Gr\u00e4f","year":"2018","journal-title":"Nat. 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