학술논문
FGL1 as a modulator of plasma D‐dimer levels: Exome‐wide marker analysis of plasma tPA, PAI‐1, and D‐dimer
Document Type
article
Author
Thibord, Florian; Song, Ci; Pattee, Jack; Rodriguez, Benjamin AT; Chen, Ming‐Huei; O’Donnell, Christopher J; Kleber, Marcus E; Delgado, Graciela E; Guo, Xiuqing; Yao, Jie; Taylor, Kent D; Ozel, Ayse Bilge; Brody, Jennifer A; McKnight, Barbara; Gyorgy, Beata; Simonsick, Eleanor; Leonard, Hampton L; Carrasquilla, Germán D; Guindo‐Martinez, Marta; Silveira, Angela; Temprano‐Sagrera, Gerard; Yanek, Lisa R; Becker, Diane M; Mathias, Rasika A; Becker, Lewis C; Raffield, Laura M; Kilpeläinen, Tuomas O; Grarup, Niels; Pedersen, Oluf; Hansen, Torben; Linneberg, Allan; Hamsten, Anders; Watkins, Hugh; Sabater‐Lleal, Maria; Nalls, Mike A; Trégouët, David‐Alexandre; Morange, Pierre‐Emmanuel; Psaty, Bruce M; Tracy, Russel P; Smith, Nicholas L; Desch, Karl C; Cushman, Mary; Rotter, Jerome I; de Vries, Paul S; Pankratz, Nathan D; Folsom, Aaron R; Morrison, Alanna C; März, Winfried; Tang, Weihong; Johnson, Andrew D
Source
Journal of Thrombosis and Haemostasis. 19(8)
Subject
Language
Abstract
BackgroundUse of targeted exome-arrays with common, rare variants and functionally enriched variation has led to discovery of new genes contributing to population variation in risk factors. Plasminogen activator-inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), and the plasma product D-dimer are important components of the fibrinolytic system. There have been few large-scale genome-wide or exome-wide studies of PAI-1, tPA, and D-dimer.ObjectivesWe sought to discover new genetic loci contributing to variation in these traits using an exome-array approach.MethodsCohort-level analyses and fixed effects meta-analyses of PAI-1 (n = 15 603), tPA (n = 6876,) and D-dimer (n = 19 306) from 12 cohorts of European ancestry with diverse study design were conducted, including single-variant analyses and gene-based burden testing.ResultsFive variants located in NME7, FGL1, and the fibrinogen locus, all associated with D-dimer levels, achieved genome-wide significance (P