Research Paper Volume 15, Issue 18 pp 9797—9808

Investigating the causal effect of Dickkopf-1 on coronary artery disease and ischemic stroke: a Mendelian randomization study

Peng-Fei Zheng1,2,3, *, , Jing-Jing Rong1,2,3, *, , Zhao-Fen Zheng1,2,3, , Zheng-Yu Liu1,2,3, , Hong-Wei Pan1,2,3, , Peng Liu4, &, ,

  • 1 Cardiology Department, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China
  • 2 Clinical Research Center for Heart Failure in Hunan Province, Furong, Changsha 410000, Hunan, China
  • 3 Institute of Cardiovascular Epidemiology, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China
  • 4 Department of Cardiology, The Central Hospital of ShaoYang, Shaoyang 422000, Hunan, China
* Equal contribution

Received: May 8, 2023       Accepted: August 21, 2023       Published: September 22, 2023
How to Cite

Copyright: © 2023 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Epidemiological investigations have indicated a correlation between elevated plasma levels of Dickkopf-related protein 1 (DKK1) and the presence of atherosclerosis. However, the exact causal relationship of DKK1 with the development of coronary artery disease (CAD) and ischemic stroke (IS) remains unclear. To address this gap, our study aimed to explore their causal association using a two-sample Mendelian randomization (MR) approach. We obtained summary statistics from genome-wide association studies (GWAS) meta-analyses conducted by Folkersen et al. and Nikpay et al., which included data from 21,758 individuals for DKK1 and 42,096 cases of CAD. Additionally, we obtained data from the FinnGen biobank analysis round 5, which included 10,551 cases of IS. Eight MR methods were employed to estimate causal effects and detect directional pleiotropy. Our findings demonstrated that genetic liability to DKK1 was associated with increased risks of CAD (odds ratio [OR]: 1.087; 95% confidence interval [CI]: 1.024–1.154; P = 0.006) and IS (OR: 1.096; 95% CI: 1.004–1.195; P = 0.039). These results establish a causal link between genetic liability to DKK1 and elevated risks of CAD and IS. Consequently, DKK1 may represent a promising therapeutic target for the prevention and treatment of CAD and IS.


DKK1: Dickkopf-1; CAD: coronary artery disease; IS: ischemic stroke; MR: mendelian randomization; IVW: inverse-variance weighted; LRP5: LDL receptor related protein 5; IL: interleukin; TNF-α: tumour necrosis factor α; MCP-1: monocyte chemoattractant protein-1; STEMI: ST-segment elevation myocardial infarction; MR-PRESSO: MR Pleiotropy RESidual Sum and Outlier; NSE-ACS: non-ST-segment elevation acute coronary syndrome; IVs: instrumental variables; TSMR: two-sample Mendelian randomization; SNPs: single nucleotide polymorphisms; LD: linkage disequilibrium; OR: odds ratio; CI: confidence interval; NF-κB: NF-kappaB.