Skip to content

Horizontal Pleiotropy (MR)

Definition
AI-generated

In Mendelian randomization, horizontal pleiotropy occurs when a genetic variant used as an instrumental variable affects the outcome through biological pathways other than the proposed exposure, violating core MR assumptions and biasing causal estimates.

Topics
Post-GWAS
Related
Genetics Genome Genomics

Why it matters in GWAS

Many loci influence multiple traits; MR methods (e.g. MR-Egger, weighted median) and LD score regression intercepts are partly motivated by detecting or accommodating such pleiotropy when interpreting summary-statistic–based inference.

Example usage

"MR-Egger intercept suggested directional pleiotropy, so we restricted instruments to liver-specific eQTLs and repeated the analysis."

Genetics Genome Genomics Horizontal Pleiotropy Linkage Disequilibrium Proxy (LD proxy) Linkage Disequilibrium (LD) LD Score Regression Mendelian Randomization (MR) Phenotype Phenome-Wide Association Study (PheWAS) Pleiotropy Vertical Pleiotropy
Related-term network

Click any node to open that term page.

Node order. The current term is first. Next come every page linked from Related terms, in the same top-to-bottom order as that list. Then new terms appear in two-hop layers: for each of those direct neighbors (in that same order), their related terms are appended if not already listed. A third pass does the same for two-hop nodes. The walk stops when a fixed maximum number of nodes is reached.

References

  • Verbanck M, Chen C-Y, Neale B, Do R. (2018). Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet.
  • Uffelmann E, et al. (2021). Genome-wide association studies. Nat Rev Methods Primers. https://doi.org/10.1038/s43586-021-00056-9
← Homozygous Horizontal Pleiotropy →

Last updated (UTC · Git history)