Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population.

Ming Yang Cao; Di Liu; Xiao Yu Zhang; Qiu Yue Tian; Qun Zhang; You Xin Wang

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Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population.

Author: Ming Yang CAO ¹ ; Di LIU ^{2
,

3} ; Xiao Yu ZHANG ^{2
,

4} ; Qiu Yue TIAN ¹ ; Qun ZHANG ⁵ ; You Xin WANG ^{2
,

6}
Author Information

1. Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China.
2. Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
3. Centre for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.
4. Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
5. Chinese Center for Disease Control and Prevention, Beijing 102206, China.
6. Centre for Precision Medicine, School of Medical and Health Sciences, Edith Cowan University, Perth 60127, Australia.
Publication Type:Journal Article
Keywords: C-reactive protein; Cardiovascular diseases; Causal inference; East Asians; Mendelian randomization
MeSH: C-Reactive Protein/metabolism*; Cardiovascular Diseases/metabolism*; Genetic Predisposition to Disease; Genotype; Humans; Japan; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors
From: Biomedical and Environmental Sciences 2022;35(2):126-132
CountryChina
Language:English
Abstract: OBJECTIVE:Traditional epidemiological studies have shown that C-reactive protein (CRP) is associated with the risk of cardiovascular diseases (CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization (MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure.
METHODS:We performed two-sample MR by using summary-level data obtained from Japanese Encyclopedia of Genetic association by Riken (JENGER), and we selected four single-nucleotide polymorphisms associated with CRP level as instrumental variables. MR estimates were calculated with the inverse-variance weighted (IVW), penalized weighted median and weighted median. MR-Egger regression was used to explore pleiotropy.
RESULTS:No significant causal association of genetically determined CRP level with ischemic stroke, atrial fibrillation or arrhythmia was found with all four MR methods (all Ps > 0.05). The IVW method indicated suggestive evidence of a causal association between CRP and congestive heart failure ( OR: 1.337, 95% CI: 1.005-1.780, P = 0.046), whereas the other three methods did not. No clear pleiotropy or heterogeneity were observed.
CONCLUSIONS:Suggestive evidence was found only in analysis of congestive heart failure; therefore, further studies are necessary. Furthermore, no causal association was found between CRP and the other three cardiovascular outcomes.