Evaluating the potential role of pleiotropy in Mendelian randomization studies

Research output: Contribution to journalArticle (Academic Journal)peer-review

661 Citations (Scopus)
508 Downloads (Pure)


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.
Original languageEnglish
Pages (from-to)R195-R208
Number of pages14
JournalHuman Molecular Genetics
Issue numberR2
Early online date16 May 2018
Publication statusPublished - 1 Aug 2018


Dive into the research topics of 'Evaluating the potential role of pleiotropy in Mendelian randomization studies'. Together they form a unique fingerprint.

Cite this