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Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

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Author(s)
Sehoon ParkSoojin LeeYaerim KimSemin ChoKwangsoo KimYong Chul KimSeung Seok HanHajeong LeeJung Pyo LeeSoryoung LeeEue-Keun ChoiKwon Wook JooChun Soo LimYon Su KimDong Ki Kim
Keimyung Author(s)
Kim, Yae Rim
Department
Dept. of Internal Medicine (내과학)
Journal Title
BMC Med
Issued Date
2021
Volume
19
Keyword
Atrial fibrillationBrainStrokeMendelian randomization
Abstract
Background:
Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis.

Methods:
The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance–weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR.

Results:
A higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta −0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E−12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta −0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome.

Conclusions:
This study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.
Keimyung Author(s)(Kor)
김예림
Publisher
School of Medicine (의과대학)
Citation
Sehoon Park et al. (2021). Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study. BMC Med, 19, 274. doi: 10.1186/s12916-021-02152-9
Type
Article
ISSN
1741-7015
Source
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02152-9
DOI
10.1186/s12916-021-02152-9
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44108
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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