TY - JOUR T1 - <em>COL18A1</em> genotypic associations with endostatin levels and clinical features in pulmonary arterial hypertension: a quantitative trait association study JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00725-2021 SP - 00725-2021 AU - Catherine E. Simpson AU - Megan Griffiths AU - Jun Yang AU - Melanie K. Nies AU - R. Dhananjay Vaidya AU - Stephanie Brandal AU - Lisa J. Martin AU - Michael W. Pauciulo AU - Katie A. Lutz AU - Anna W. Coleman AU - Eric D. Austin AU - D. Dunbar Ivy AU - William C. Nichols AU - Allen D. Everett AU - Paul M. Hassoun AU - Rachel L. Damico Y1 - 2022/01/01 UR - http://openres.ersjournals.com/content/early/2022/05/05/23120541.00725-2021.abstract N2 - Endostatin (ES) is a circulating peptide derived from collagen XVIII, alpha 1 (COL18A1) known to inhibit angiogenesis [1, 2]. Decreased angiogenesis is a feature of pulmonary arterial hypertension (PAH) in animal models [3] and human subjects [4]. Our group has reported strong associations between circulating ES levels and hemodynamics and survival in PAH [5–7]. We have also reported that a missense variant in COL18A1, which encodes ES, confers lower ES and longer survival, suggesting variation within the gene contributes to circulating levels [5]. With this study, we assessed COL18A1 variant associations with clinical phenotypes and outcomes, including COL18A1 associations with circulating ES levels, in a large, multicenter PAH cohort in which we previously investigated ES as a prognostic biomarker [6].FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Catherine E. Simpson reports support for the present manuscript received from NIH/NHLBI grants.Conflict of interest: Megan Griffiths reports support for the present manuscript received from NIH/NHLBI grants.Conflict of interest: Jun Yang has nothing to disclose.Conflict of interest: Melanie K. Nies has nothing to disclose.Conflict of interest: Dhananjay Vaidya reports receiving grants or contacts outside the submitted work from National Institutes of Health.Conflict of interest: Stephanie Brandal has nothing to disclose.Conflict of interest: Lisa J. Martin reports support for the present manuscript received from NIH/NHLBI grants.Conflict of interest: Michael W. Pauciulo has nothing to disclose.Conflict of interest: Katie A. Lutz has nothing to disclose.Conflict of interest: Anna W. Coleman has nothing to disclose.Conflict of interest: Eric D. Austin reports support for the present manuscript received from NIH/NHLBI grants. Grants or contracts received from CMREF, outside the submitted work.Conflict of interest: D. Dunbar Ivy reports support for the present manuscript received from NIH/NHLBI grants. Consulting fees received from The University of Colorado contracts with Actelion, Altavant, Bayer, and Gossamer Bio, outside the submitted work.Conflict of interest: William C. Nichols reports support for the present manuscript received from NIH/NHLBI grants.Conflict of interest: Allen D. Everett reports support for the present manuscript received from NIH/NHLBI grants.Conflict of interest: Paul M. Hassoun reports receiving grants or contacts outside the submitted work from NIH/NHLBI. Participation on a Data Safety Monitoring Board or Advisory Board for PMH serves on a scientific Advisory Board for MSD. This activity is unrelated to the current work.Conflict of interest: Rachel L. Damico reports support for the present manuscript received from NIH/NHLBI grants. ER -