Science China Life Sciences

, Volume 62, Issue 6, pp 758–770 | Cite as

Mendelian randomization studies on atherosclerotic cardiovascular disease: evidence and limitations

  • Qin HuEmail author
  • Panpan Hao
  • Qiji Liu
  • Mei Dong
  • Yaoqin Gong
  • Cheng Zhang
  • Yun ZhangEmail author


Epidemiological research has revealed a galaxy of biomarkers, such as genes, molecules or traits, which are associated with increased risk of atherosclerotic cardiovascular diseases (ASCVD). However, the etiological basis remains poorly characterized. Mendelian randomization (MR) involves the use of observational genetic data to ascertain the roles of disease-associated risk factors and, in particular, differentiate those reflecting the presence or severity of a disease from those contributing causally to a disease. Over the past decade, MR has evolved into a fruitful approach to clarifying the causal relation of a biomarker with ASCVD and to verifying potential therapeutic targets for ASCVD. In this review, we selected high-quality MR studies on ASCVD, examined the causal relationship of a series of biomarkers with ASCVD, and elucidated the role of MR in validating biomarkers as a therapeutic target by comparing the results from MR studies and randomized clinical trials (RCTs) for the treatment of ASCVD. The good agreement between the results derived by MR and RCTs suggests that MR could be performed as a screening process before novel drug development. However, when designing and interpreting a MR study, the assumptions and limitations inherent in this approach should be taken into account. Novel methodological developments, such as sensitivity analysis, will help to strengthen the validity of MR studies.

Mendelian randomization atherosclerotic cardiovascular disease causality therapeutic target 


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This work was supported by the State Key Program of National Natural Science of China (81530014), the National Natural Science Foundation of China (81370410, 81425004, 81770442, 81571689) and the Taishan Scholars Program of Shandong province, China.

Supplementary material

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Supplementary material, approximately 129 KB.
11427_2019_9537_MOESM2_ESM.docx (13 kb)
Legend to Supplemental Figure 1
11427_2019_9537_MOESM3_ESM.docx (16 kb)
Supplemental Table 1. Consistency between RCTs and MRs in identifying causal risk factors for ASCVD


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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education of China, Ministry of Health of China and Chinese Academy of Medical Sciences, and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong UniversityJinanChina
  2. 2.Department of Medical Genetics, School of Medicine, Key Laboratory of Experimental Teratology, Ministry of EducationShandong UniversityJinanChina

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