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--- mendelian_randomization [2024/06/07 02:50] – created - external edit 127.0.0.1
+++ mendelian_randomization [2025/07/02 19:08] (current) – administrador
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-Mendelian randomization is a method of using measured variation in genes of known function to examine the causal effect of a modifiable exposure on disease in observational studies .
+====== Mendelian Randomization ======
+**Mendelian Randomization (MR)** is a method in genetic epidemiology that uses genetic variants as proxies (instrumental variables) to test for causal relationships between modifiable exposures (e.g., biomarkers, behaviors) and disease outcomes.
+===== 🧬 Definition =====
+Mendelian Randomization is an analytical approach that leverages the random allocation of genetic variants at conception—analogous to a randomized controlled trial—to assess whether an observed association between a risk factor and an outcome is likely to be causal.
+===== 🧪 Key Concepts =====
+  * **Instrumental Variables**: Genetic variants (usually single-nucleotide polymorphisms, SNPs) associated with an exposure of interest.
+  * **Causal Inference**: If the genetic variant influences the disease **only through** the exposure, a causal link can be inferred.
+  * **Three Assumptions**:
+    - The genetic variant is associated with the exposure.
+    - The genetic variant is not associated with confounders.
+    - The genetic variant affects the outcome only through the exposure (no pleiotropy).
+===== 📊 Applications =====
+  * Determining if elevated LDL cholesterol causally increases cardiovascular disease risk.
+  * Exploring whether inflammation-related genes are causally linked to intracerebral hemorrhage (ICH).
+  * Investigating the effect of lifestyle factors (e.g., alcohol use, BMI) on various diseases.
+===== ⚠️ Limitations =====
+  * Horizontal pleiotropy can violate assumptions.
+  * Weak instruments may lead to biased estimates.
+  * Population stratification can introduce confounding if not controlled.
+===== 📚 Example =====
+In a study of neuroinflammation and ICH, MR can test if genetic variants that increase inflammatory markers (e.g., IL-6) also increase the risk of intracerebral hemorrhage—suggesting a causal role of inflammation in ICH pathophysiology.