A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study

BackgroundObservational studies have suggested that irritability is associated with a higher risk of cardiovascular disease (CVD). However, the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of irritability with CV...

Full description

Bibliographic Details
Main Authors: Dihui Cai, Yin Fu, Yongfei Song, Hui Lin, Yanna Ba, Jiangfang Lian
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1174329/full
_version_ 1797814165386035200
author Dihui Cai
Yin Fu
Yongfei Song
Hui Lin
Yanna Ba
Jiangfang Lian
author_facet Dihui Cai
Yin Fu
Yongfei Song
Hui Lin
Yanna Ba
Jiangfang Lian
author_sort Dihui Cai
collection DOAJ
description BackgroundObservational studies have suggested that irritability is associated with a higher risk of cardiovascular disease (CVD). However, the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of irritability with CVD risk.MethodsA two-sample MR analysis was performed to confirm the causal association of irritability with the risk of several common CVDs. The exposure data were derived from the UK biobank involving 90,282 cases and 232,386 controls, and outcome data were collected from the published genome-wide association studies (GWAS) and FinnGen database. Inverse-variance weighted (IVW), MR-Egger, and weighted median methods were performed to assess the causal association. Furthermore, the mediating effect of smoking, insomnia, and depressed affect was explored by using a two-step MR.ResultsThe MR analysis indicated that genetically predicted irritability increased the risk of CVD, including coronary artery disease (CAD) (Odds ratio, OR: 2.989; 95% confidence interval, CI: 1.521–5.874, p = 0.001), myocardial infarction (MI) (OR: 2.329, 95% CI: 1.145–4.737, p = 0.020), coronary angioplasty (OR: 5.989, 95% CI: 1.696–21.153, p = 0.005), atrial fibrillation (AF) (OR: 4.646, 95% CI: 1.268–17.026, p = 0.02), hypertensive heart disease (HHD) (OR: 8.203; 95% CI: 1.614–41.698, p = 0.011), non-ischemic cardiomyopathy (NIC) (OR: 5.186; 95% CI: 1.994–13.487, p = 0.001), heart failure (HF) (OR: 2.253; 95% CI: 1.327–3.828, p = 0.003), stroke (OR: 2.334; 95% CI: 1.270–4.292, p = 0.006), ischemic stroke (IS) (OR: 2.249; 95% CI: 1.156–4.374, p = 0.017), and ischemic stroke of large-artery atherosclerosis ISla (OR: 14.326; 95% CI: 2.750–74.540, p = 0.002). The analysis also indicated that smoking, insomnia, and depressed affect play an important role in the process of irritability leading to cardiovascular disease.ConclusionOur findings support the first genetic evidence of the causality of genetically predicted irritability with the risk of developing into CVDs. Our results deliver a viewpoint that more early active interventions to manage an individual's anger and related unhealthy lifestyle habits are needed to prevent the occurrence of adverse cardiovascular events.
first_indexed 2024-03-13T08:03:33Z
format Article
id doaj.art-c1d77e3c773b48ddaf72cb1706bec848
institution Directory Open Access Journal
issn 2297-055X
language English
last_indexed 2024-03-13T08:03:33Z
publishDate 2023-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cardiovascular Medicine
spelling doaj.art-c1d77e3c773b48ddaf72cb1706bec8482023-06-01T09:54:26ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-05-011010.3389/fcvm.2023.11743291174329A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization studyDihui CaiYin FuYongfei SongHui LinYanna BaJiangfang LianBackgroundObservational studies have suggested that irritability is associated with a higher risk of cardiovascular disease (CVD). However, the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of irritability with CVD risk.MethodsA two-sample MR analysis was performed to confirm the causal association of irritability with the risk of several common CVDs. The exposure data were derived from the UK biobank involving 90,282 cases and 232,386 controls, and outcome data were collected from the published genome-wide association studies (GWAS) and FinnGen database. Inverse-variance weighted (IVW), MR-Egger, and weighted median methods were performed to assess the causal association. Furthermore, the mediating effect of smoking, insomnia, and depressed affect was explored by using a two-step MR.ResultsThe MR analysis indicated that genetically predicted irritability increased the risk of CVD, including coronary artery disease (CAD) (Odds ratio, OR: 2.989; 95% confidence interval, CI: 1.521–5.874, p = 0.001), myocardial infarction (MI) (OR: 2.329, 95% CI: 1.145–4.737, p = 0.020), coronary angioplasty (OR: 5.989, 95% CI: 1.696–21.153, p = 0.005), atrial fibrillation (AF) (OR: 4.646, 95% CI: 1.268–17.026, p = 0.02), hypertensive heart disease (HHD) (OR: 8.203; 95% CI: 1.614–41.698, p = 0.011), non-ischemic cardiomyopathy (NIC) (OR: 5.186; 95% CI: 1.994–13.487, p = 0.001), heart failure (HF) (OR: 2.253; 95% CI: 1.327–3.828, p = 0.003), stroke (OR: 2.334; 95% CI: 1.270–4.292, p = 0.006), ischemic stroke (IS) (OR: 2.249; 95% CI: 1.156–4.374, p = 0.017), and ischemic stroke of large-artery atherosclerosis ISla (OR: 14.326; 95% CI: 2.750–74.540, p = 0.002). The analysis also indicated that smoking, insomnia, and depressed affect play an important role in the process of irritability leading to cardiovascular disease.ConclusionOur findings support the first genetic evidence of the causality of genetically predicted irritability with the risk of developing into CVDs. Our results deliver a viewpoint that more early active interventions to manage an individual's anger and related unhealthy lifestyle habits are needed to prevent the occurrence of adverse cardiovascular events.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1174329/fullcardiovascular diseaseirritabilitycoronary artery diseaseheart failureMendelian randomization
spellingShingle Dihui Cai
Yin Fu
Yongfei Song
Hui Lin
Yanna Ba
Jiangfang Lian
A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study
Frontiers in Cardiovascular Medicine
cardiovascular disease
irritability
coronary artery disease
heart failure
Mendelian randomization
title A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study
title_full A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study
title_fullStr A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study
title_full_unstemmed A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study
title_short A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study
title_sort causal relationship between irritability and cardiovascular diseases a mendelian randomization study
topic cardiovascular disease
irritability
coronary artery disease
heart failure
Mendelian randomization
url https://www.frontiersin.org/articles/10.3389/fcvm.2023.1174329/full
work_keys_str_mv AT dihuicai acausalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT yinfu acausalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT yongfeisong acausalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT huilin acausalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT yannaba acausalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT jiangfanglian acausalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT dihuicai causalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT yinfu causalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT yongfeisong causalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT huilin causalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT yannaba causalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy
AT jiangfanglian causalrelationshipbetweenirritabilityandcardiovasculardiseasesamendelianrandomizationstudy