Evaluating the potential role of pleiotropy in Mendelian randomization studies
By Gibran Hemani, J. Bowden, George Davey Smith. Human Molecular Genetics, 2018
1,292 citations recorded by the source corpus.
Abstract Pleiotropy, the phenomenon of a single genetic variant influencing multiple traits, is likely widespread in the human genome. If pleiotropy arises because the single nucleotide polymorphism (SNP) influences one trait, which in turn influences another (‘vertical pleiotropy’), then Mendelian randomization (MR) can be used to estimate the causal influence between the traits. Of prime focus among the many limitations to MR is the unprovable assumption that apparent pleiotropic associations are mediated by the exposure (i.e. reflect vertical pleiotropy), and do not arise due to SNPs influencing the two traits through independent pathways (‘horizontal pleiotropy’). The burgeoning treasure trove of genetic associations yielded through genome wide association studies makes for a tantalizing prospect of phenome-wide causal inference. Recent years have seen substantial attention devoted to the problem of horizontal pleiotropy, and in this review we outline how newly developed methods can be used together to improve the reliability of MR.
Subfields: Genetics
View Paper: https://www.semanticscholar.org/paper/9f949384ef1e579a7c131fd095721e8352f1e2b2
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In Genetics
- E. Sanderson
- George Davey Smith
- J. Bowden
- Michael Holmes
- N. Davies
- T. Palmer
- Mika Ala-Korpela
- B. Ference
Citations in the corpus
- Mendelian randomisation for mediation analysis: current methods and challenges for implementation (2019, background): “Bias due to pleiotropy has been discussed extensively in the literature [41, 42].”
- Meta‐analysis and Mendelian randomization: A review (2019, background): “Unfortunately, due to the sheer number of variants that can now be easily included in such MR analyses, often with limited knowledge of their functional role, it is increasingly likely that some do not meet the IV assumptions due to a phenomenon known as horizontal pleiotropy.(14) This occurs when a”
- Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis (2020, methodology): “To further account for potential unbalanced horizontal pleiotropy in the multivariable MR analysis, we also conducted multivariable MR-Egger analyses [56,57].”