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An effect of one gene or genetic variant on multiple distinguishable phenotypic traits. It can constrain evolution when effects oppose simultaneous improvement, or facilitate coordinated improvement when their directions align with natural selection. Distinguish a single causal change from several linked changes.

Population stratification is systematic variation in allele frequencies between subpopulations. If those subpopulations also differ in outcome causes, genetic variant associations can exhibit confounding, violating instrumental-variable independence in Mendelian randomization.

Mapping inherited differences in a quantitative phenotypic trait to genomic intervals through segregation and genetic recombination. A detected interval need not contain only one causal gene or genetic variant.

An assembled genome used as a coordinate system for mapping sequence measurements and comparing genetic variants. A reference is a chosen representation rather than all variation within a species.

Two-sample Mendelian randomization combines genetic variant associations with an exposure estimated in one sample and their associations with an outcome estimated in another. It requires the instrumental variable assumptions and compatible associations across the populations; sample overlap can change the behaviour of weak instruments.

This weighted median of genetic variant ratio estimates consistently estimates a common causal effect when more than half of its asymptotic weight comes from valid instrumental variables, subject to the usual sampling regularity conditions. It is a sensitivity analysis for horizontal pleiotropy, not an unconditional guarantee of validity.