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Joined 2026-09-21 Message
Incoming links: Mendelian randomization
Genetic variant 2026-09-28
A genetic variant is a heritable difference in a DNA sequence relative to a chosen reference. Genetic variants can be used as instrumental variables in Mendelian randomization when the required causal assumptions are credible.
Horizontal pleiotropy 2026-09-28
Horizontal pleiotropy occurs when a genetic instrument affects an outcome through a pathway other than the exposure under study. It violates the exclusion restriction in Mendelian randomization.
Past exam of the mathematics course of the University of Cambridge 2021 iii Paper 207 2 e Solution 2026-09-28
Three useful extensions are:
- Replicate the bidirectional Mendelian randomization in independent, larger cohorts and ancestries, using nonoverlapping discovery and outcome samples to improve precision and reduce winner's-curse and population-specific artifacts.
- Apply pleiotropy-robust analyses such as weighted-median, mode-based, and MR-Egger estimates, inspect heterogeneity and leave-one-variant-out results, and use biologically distinct instrument sets. Agreement despite different sensitivities to invalid instruments strengthens the exclusion restriction.
- Triangulate with a design based on an independent source of causal variation, such as compulsory-schooling-law changes or another natural experiment, and with longitudinal refractive measurements. Agreement across designs with different biases is stronger evidence than enlarging one genetic analysis alone.
Past exam of the mathematics course of the University of Cambridge 2022 iii Paper 207 1 1 5 Solution 2026-09-28
The overall odds ratio is with 95% interval , so there is little evidence for an average effect. The estimate changes sharply across residual-vitamin-D strata: it is in the deficient group, in the insufficient group, and close to one in the two higher groups. The pattern is consistent with effect modification: raising vitamin D may reduce mortality among deficient people but offer little benefit once concentration is adequate. The claim still depends on the Mendelian randomization assumptions and should account for the fact that several subgroup estimates were examined.