Evaluating the potential role of pleiotropy in Mendelian randomization studies

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...

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Vydáno v:Human molecular genetics Ročník 27; číslo R2; s. R195 - R208
Hlavní autoři: Hemani, Gibran, Bowden, Jack, Davey Smith, George
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Oxford University Press 01.08.2018
Témata:
Animals
Genetic Pleiotropy - genetics
Genetic Pleiotropy - physiology
Genetic Variation
Genome, Human
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis - methods
Phenotype
Polymorphism, Single Nucleotide - genetics
Reproducibility of Results
ISSN:0964-6906, 1460-2083, 1460-2083
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/ddy163