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. 2021 Jul 13;9(2):122-132.
doi: 10.1007/s40484-020-0216-3. Epub 2020 Oct 21.

Mendelian randomization and pleiotropy analysis

Xiaofeng Zhu  1
Affiliations

Mendelian randomization and pleiotropy analysis

Xiaofeng Zhu. Quant Biol. .

Abstract

Background: Mendelian randomization (MR) analysis has become popular in inferring and estimating the causality of an exposure on an outcome due to the success of genome wide association studies. Many statistical approaches have been developed and each of these methods require specific assumptions.

Results: In this article, we review the pros and cons of these methods. We use an example of high-density lipoprotein cholesterol on coronary artery disease to illuminate the challenges in Mendelian randomization investigation.

Conclusion: The current available MR approaches allow us to study causality among risk factors and outcomes. However, novel approaches are desirable for overcoming multiple source confounding of risk factors and an outcome in MR analysis.

Keywords: Mendelian randomization; causality; confounding; instrumental variable; summary statistics.

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Conflict of interest statement

COMPLIANCE WITH ETHICS GUIDELINES The author Xiaofeng Zhu declare that he has no conflict of interests.

Figures

Figure 1.
Figure 1.. Comparison between RCT and MR designs.
Figure 2.
Figure 2.. A causal path diagram for multiple instrumental variables.
Figure 3.
Figure 3.. The relationships of genetic variants, exposure and outcome.
(A) Mediation: the causal variant lies on the causal path to Y. (B) Horizontal pleiotropy: the causal variant affects both E and Y. (C) Colocalization: two different causal variants at one locus affect E and Y. The red star represents the causal variant and S represents genetic markers.
Figure 4.
Figure 4.. The two path diagrams for HDL-C and CAD.
(A) There is no separate path through TG. (B) There is a separate path through TG.
See this image and copyright information in PMC

References

    1. Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B,Shike M, Weissfeld J, Burt R, Cooper MR, et al. (2000) Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. N. Engl. J. Med, 342, 1149–1155 - PubMed
    1. The Heart Outcomes Prevention Evaluation Study Investigators.(2000) Vitamin E supplementation and cardiovascular events in high-risk patients. N. Engl. J. Med, 342, 154–160 - PubMed
    1. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group.(1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med, 330, 1029–1035 - PubMed
    1. Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ and Gaziano JM (2008) Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA, 300, 2123–2133 - PMC - PubMed
    1. Davey Smith G. and Ebrahim S. (2001) Epidemiology–is it time to call it a day? Int. J. Epidemiol, 30, 1–11 - PubMed