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Página principal > Artículos > Artículos publicados > Integrated GWAS and Gene Expression Suggest ORM1 as a Potential Regulator of Plasma Levels of Cell-Free DNA and Thrombosis Risk |
Fecha: | 2022 |
Resumen: | Plasma cell-free DNA (cfDNA) is a surrogate marker of neutrophil extracellular traps (NETs) that contribute to immunothrombosis. There is growing interest about the mechanisms underlying NET formation and elevated cfDNA, but little is known about the factors involved. We aimed to identify genes involved in the regulation of cfDNA levels using data from the Genetic Analysis of Idiopathic Thrombophilia (GAIT-2) Project. Imputed genotypes, whole blood RNA-Seq data, and plasma cfDNA quantification were available for 935 of the GAIT-2 participants from 35 families with idiopathic thrombophilia. We performed heritability and GWAS analysis for cfDNA. The heritability of cfDNA was 0. 26 (p 3. 7106), while the GWAS identified a significant association (rs1687391, p 3. 551010) near the ORM1 gene, on chromosome 9. An eQTL (expression quantitative trait loci) analysis revealed a significant association between the lead GWAS variant and the expression of ORM1 in whole blood (p 6. 14109). Additionally, ORM1 expression correlated with levels of cfDNA (p 4. 38104). Finally, genetic correlation analysis between cfDNA and thrombosis identified a suggestive association (?g 0. 43, p 0. 089). All in all, we show evidence of the role of ORM1 in regulating cfDNA levels in plasma, which might contribute to the susceptibility to thrombosis through mechanisms of immunothrombosis. |
Ayudas: | Instituto de Salud Carlos III PI14/00582 Instituto de Salud Carlos III PI17/00059 Instituto de Salud Carlos III CP17/00142 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR1736 Agència de Gestió d'Ajuts Universitaris i de Recerca FI2017B_00673 |
Nota: | Altres ajuts: CERCA Programme, Generalitat de Catalunya; Fundación Española de Trombosis y Hemostasia; European Social Fund. |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Immunothrombosis ; Neutrophil extracellular traps ; α-1-acid glycoprotein 1 ; Expression quantitative trait loci |
Publicado en: | Thrombosis and Haemostasis, Vol. 122 Núm. 6 (january 2022) , p. 1027-1039, ISSN 2567-689X |
13 p, 2.5 MB |