A two-sample Mendelian randomization study of atherosclerosis and dementia

Qiaoyun Zhang; Guangheng Wu; Xiaoyu Zhang; Sheng Wang; Youxin Wang

doi:10.1016/j.isci.2023.108325

A two-sample Mendelian randomization study of atherosclerosis and dementia

iScience. 2023 Oct 24;26(11):108325. doi: 10.1016/j.isci.2023.108325. eCollection 2023 Nov 17.

Authors

Qiaoyun Zhang^{1

2}, Guangheng Wu², Xiaoyu Zhang³, Sheng Wang¹, Youxin Wang^{4

5

6}

Affiliations

¹ Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
² School of Public Health, Capital Medical University, Beijing, China.
³ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
⁴ School of Public Health, North China University of Science and Technology, Tangshan, China.
⁵ Beijing Key Laboratory of Clinical Epidemiology, Beijing, China.
⁶ Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.

Abstract

The causality between atherosclerosis and dementia remains unclear. This study aimed to explore the causal effect of atherosclerosis related indicators on dementia risk based on two-sample Mendelian randomization (MR) using summary statistics of genome-wide association studies (GWASs). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by different sensitivity analyses. Suggestive evidence indicated that peripheral arterial disease (PAD) (odds ratio (OR): 0.864, 95% confidence interval (CI): 0.797-0.937), coronary atherosclerosis (CoAS) (OR: 0.927, 95% CI: 0.860-0.998) and atherosclerosis, excluding cerebral, coronary, and PAD (ATHSCLE) (OR: 0.812, 95% CI: 0.725-0.909) were inversely associated with the risk of AD. The sensitivity analysis confirmed a suggestive reverse effect of ATHSCLE on the risk of frontotemporal dementia (FTD) (OR, 0.812, 95% CI, 0.725-0.909). Findings provide suggestive evidence that PAD, CoAS, and ATHSCLE might be associated with the risk of AD or FTD, which requires further exploration in larger samples.

Keywords: Cardiovascular medicine; Clinical neuroscience; Human genetics; Public health.