Mendelian randomization study reveals a causal relationship between coronary artery disease and cognitive impairment

Shihan Xu; Yanfei Liu; Qing Wang; Fenglan Liu; Fengqin Xu; Yue Liu

doi:10.3389/fcvm.2023.1150432

Mendelian randomization study reveals a causal relationship between coronary artery disease and cognitive impairment

Front Cardiovasc Med. 2023 May 23:10:1150432. doi: 10.3389/fcvm.2023.1150432. eCollection 2023.

Authors

Shihan Xu^#^{1

2}, Yanfei Liu^#^{1

2}, Qing Wang^{1

2}, Fenglan Liu³, Fengqin Xu^{1

2}, Yue Liu²

Affiliations

¹ The Second Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
² National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
³ Graduate School of Guangdong Pharmaceutical University, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Growing evidence suggests that Coronary artery disease (CAD) is associated with cognitive impairment. However, these results from observational studies was not entirely consistent, with some detecting no such association. And it is necessary to explore the causal relationship between CAD and cognitive impairment.

Objective: We aimed to explore the potential causal relationship between CAD and cognitive impairment by using bidirectional two-sample mendelian randomization (MR) analyses.

Methods: Instrument variants were extracted according to strict selection criteria. And we used publicly available summary-level GWAS data. Five different methods of MR [random-effect inverse-variance weighted (IVW), MR Egger, weighted median, weighted mode and Wald ratio] were used to explore the causal relationship between CAD and cognitive impairment.

Results: There was little evidence to support a causal effect of CAD on cognitive impairment in the forward MR analysis. In the reverse MR analyses, We detect causal effects of fluid intelligence score (IVW: β = -0.12, 95% CI of -0.18 to -0.06, P = 6.8 × 10^-5), cognitive performance (IVW: β = -0.18, 95% CI of -0.28 to -0.08, P = 5.8 × 10^-4) and dementia with lewy bodies (IVW: OR = 1.07, 95% CI of 1.04-1.10, P = 1.1 × 10^-5) on CAD.

Conclusion: This MR analysis provides evidence of a causal association between cognitive impairment and CAD. Our findings highlight the importance of screening for coronary heart disease in patients of cognitive impairment, which might provide new insight into the prevention of CAD. Moreover, our study provides clues for risk factor identification and early prediction of CAD.

Keywords: causal effect; cognitive impairment; coronary artery disease; genome-wide association studies; mendelian randomization.

Grants and funding

This study is supported through the key project of scientific and technological innovation project sponsored by Chinese Academy of Chinese Medical Sciences (grant no. CI2021A01406) and the Special Project for Outstanding Young Talents of China Academy of Chinese Medical Sciences (grant no. ZZ15-YQ-017 and ZZ13-YQ-001-A1).