Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases

Major depressive disorder (MDD) is phenotypically associated with cardiovascular diseases (CVD). We aim to investigate mechanisms underlying relationships between MDD and CVD in the context of shared genetic variations. Polygenic overlap analysis was used to test genetic correlation and to analyze s...

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Autores principales:	Fuquan Zhang, Hongbao Cao, Ancha Baranova
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	major depressive disorder cardiovascular disease Mendelian randomization polygenic overlap stroke Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/d5c942bd4e6142a2a1a63e702a6033d0
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spelling	oai:doaj.org-article:d5c942bd4e6142a2a1a63e702a6033d02021-11-11T05:55:23ZShared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases2297-055X10.3389/fcvm.2021.735136https://doaj.org/article/d5c942bd4e6142a2a1a63e702a6033d02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.735136/fullhttps://doaj.org/toc/2297-055XMajor depressive disorder (MDD) is phenotypically associated with cardiovascular diseases (CVD). We aim to investigate mechanisms underlying relationships between MDD and CVD in the context of shared genetic variations. Polygenic overlap analysis was used to test genetic correlation and to analyze shared genetic variations between MDD and seven cardiovascular outcomes (coronary artery disease (CAD), heart failure, atrial fibrillation, stroke, systolic blood pressure, diastolic blood pressure, and pulse pressure measurement). Mendelian randomization analysis was used to uncover causal relationships between MDD and cardiovascular traits. By cross-trait meta-analysis, we identified a set of genomic loci shared between the traits of MDD and stroke. Putative causal genes for MDD and stroke were prioritized by fine-mapping of transcriptome-wide associations. Polygenic overlap analysis pointed toward substantial genetic variation overlap between MDD and CVD. Mendelian randomization analysis indicated that genetic liability to MDD has a causal effect on CAD and stroke. Comparison of genome-wide genes shared by MDD and CVD suggests 20q12 as a pleiotropic region conferring risk for both MDD and CVD. Cross-trait meta-analyses and fine-mapping of transcriptome-wide association signals identified novel risk genes for MDD and stroke, including RPL31P12, BORSC7, PNPT11, and PGF. Many genetic variations associated with MDD and CVD outcomes are shared, thus, pointing that genetic liability to MDD may also confer risk for stroke and CAD. Presented results shed light on mechanistic connections between MDD and CVD phenotypes.Fuquan ZhangFuquan ZhangFuquan ZhangHongbao CaoAncha BaranovaAncha BaranovaFrontiers Media S.A.articlemajor depressive disordercardiovascular diseaseMendelian randomizationpolygenic overlapstrokeDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	major depressive disorder cardiovascular disease Mendelian randomization polygenic overlap stroke Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	major depressive disorder cardiovascular disease Mendelian randomization polygenic overlap stroke Diseases of the circulatory (Cardiovascular) system RC666-701 Fuquan Zhang Fuquan Zhang Fuquan Zhang Hongbao Cao Ancha Baranova Ancha Baranova Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases
description	Major depressive disorder (MDD) is phenotypically associated with cardiovascular diseases (CVD). We aim to investigate mechanisms underlying relationships between MDD and CVD in the context of shared genetic variations. Polygenic overlap analysis was used to test genetic correlation and to analyze shared genetic variations between MDD and seven cardiovascular outcomes (coronary artery disease (CAD), heart failure, atrial fibrillation, stroke, systolic blood pressure, diastolic blood pressure, and pulse pressure measurement). Mendelian randomization analysis was used to uncover causal relationships between MDD and cardiovascular traits. By cross-trait meta-analysis, we identified a set of genomic loci shared between the traits of MDD and stroke. Putative causal genes for MDD and stroke were prioritized by fine-mapping of transcriptome-wide associations. Polygenic overlap analysis pointed toward substantial genetic variation overlap between MDD and CVD. Mendelian randomization analysis indicated that genetic liability to MDD has a causal effect on CAD and stroke. Comparison of genome-wide genes shared by MDD and CVD suggests 20q12 as a pleiotropic region conferring risk for both MDD and CVD. Cross-trait meta-analyses and fine-mapping of transcriptome-wide association signals identified novel risk genes for MDD and stroke, including RPL31P12, BORSC7, PNPT11, and PGF. Many genetic variations associated with MDD and CVD outcomes are shared, thus, pointing that genetic liability to MDD may also confer risk for stroke and CAD. Presented results shed light on mechanistic connections between MDD and CVD phenotypes.
format	article
author	Fuquan Zhang Fuquan Zhang Fuquan Zhang Hongbao Cao Ancha Baranova Ancha Baranova
author_facet	Fuquan Zhang Fuquan Zhang Fuquan Zhang Hongbao Cao Ancha Baranova Ancha Baranova
author_sort	Fuquan Zhang
title	Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases
title_short	Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases
title_full	Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases
title_fullStr	Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases
title_full_unstemmed	Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases
title_sort	shared genetic liability and causal associations between major depressive disorder and cardiovascular diseases
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d5c942bd4e6142a2a1a63e702a6033d0
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Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases

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