Unpublished draft

Causal inference frameworks in biology

I noticed that when doctors, economists, and computer scientists try to reason about the effects of genes, their thinking bottoms out in probabilities or effect sizes. Something like “this gene causes you to have 50% higher risk of cancer” or “these alleles will give you +5 IQ points”.

I feel uneasy seeing these kinds of claims, but it’s hard to say exactly why. These kinds of causal claims are very different from the ones we make in the lab. If I had to put my finger on it, I’d call them “predictive causality”, as opposed to “mechanistic causality”.

Different kinds of causal frameworks have already been described by philosophers of science, so let’s look at them.

Some of the major frameworks and named approaches are:

FrameworkMain ideaTypical use in biology
Interventionism (Woodward)X causes Y if manipulating X changes YKnockouts, CRISPR perturbations, drug treatments
Manipulationist causation (Pearl/Woodward tradition)Causation defined through interventions rather than correlationsGenetic perturbation studies
Potential Outcomes Framework (Rubin Causal Model)Compare outcome under treatment vs no treatmentClinical trials, increasingly genomics
Structural Causal Models (Pearl)Directed acyclic graphs and structural equationsEpidemiology, systems biology, genomics
INUS conditions (Mackie)Cause is an insufficient but necessary part of an unnecessary but sufficient complexMultifactorial disease causation
Mechanistic causationExplain causal relations by identifying entities and activities producing an effectDominant style in molecular biology
Probabilistic causation (Suppes)Causes raise probabilities of effectsCancer epidemiology, risk factors
Counterfactual causation (Lewis)If X had not occurred, Y would not have occurredEvolutionary biology, epidemiology
Actual causationWhich particular event caused a particular outcome?Precision medicine, pathology
Causal network inferenceInfer causal graph from observational dataTranscriptomics, signaling networks
Dynamical systems causationCausation as state transitions in dynamical systemsDevelopmental biology, physiology
Information-theoretic causalityCausal influence measured via information flowNeuroscience, systems biology