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

BMC Medicine

Sehoon Park¹  Yon Su Kim²  Hajeong Lee³  Yong Chul Kim³  Semin Cho⁴  Eue-Keun Choi⁴  Soryoung Lee⁴  Soojin Lee⁵  Dong Ki Kim⁶  Kwon Wook Joo⁶  Seung Seok Han⁷  Chun Soo Lim⁸  Jung Pyo Lee⁸  Yaerim Kim⁹  Kwangsoo Kim^1,10 

[1] Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea;Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do, Seongnam, Korea;Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea;Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea;Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, 03080, Seoul, Korea;Kidney Research Institute, Seoul National University, Seoul, Korea;Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea;Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea;Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, 03080, Seoul, Korea;Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea;Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, 03080, Seoul, Korea;Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea;Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea;Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, 03080, Seoul, Korea;Kidney Research Institute, Seoul National University, Seoul, Korea;Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea;Kidney Research Institute, Seoul National University, Seoul, Korea;Department of Internal Medicine, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Uijeongbu, Korea;Kidney Research Institute, Seoul National University, Seoul, Korea;Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea;Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea;Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea;

关键词: Atrial fibrillation;    Brain;    Stroke;    Mendelian randomization;   

DOI  :  10.1186/s12916-021-02152-9

来源: Springer

【 摘 要 】

BackgroundAtrial 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.MethodsThe 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.ResultsA 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.ConclusionsThis 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.

【 授权许可】

CC BY