Quantitative Genetics and Complex Traits
From single genes to trait architecture
Phenotypic variance decomposition
For a trait , a useful starting model is , with genetic variance often decomposed into additive, dominance, and epistatic components. The additive component is central for prediction and response to selection.
Key terms in quantitative genetics
Gene-by-environment interaction
The effect of a genotype can depend on environment, and environmental sensitivity can itself be heritable. This means that genetic effect sizes are not universal constants; they are often conditional on ancestry, age, sex, tissue, diet, pathogens, and social context.
Interpretive caution
Heritability is not immutability. A highly heritable trait can still be strongly modified by environment, and a low-heritability trait can still have major individual genetic causes.
Single-gene versus complex-trait analysis
Single-gene traits
- Often large effect sizes
- Mendelian or near-Mendelian segregation
- Family-based mapping is powerful
Complex traits
- Many variants of small effect
- Strong environmental and demographic confounding
- Requires large cohorts and careful statistical correction
Which quantity is most directly relevant for short-term response to selection?
Additive genetic variance, summarized by narrow-sense heritability, best predicts response to selection in standard models.
Correct answer: Narrow-sense heritability
Why can a polygenic score transfer poorly across populations?
Prediction depends on the training population’s genetic background and environmental context.
Correct answer: Because linkage disequilibrium, allele frequencies, effect sizes, environment, and ancestry-specific architecture can differ across populations.
Designing a GWAS interpretation pipeline
-
1
Confirm phenotype definition and study design.
-
2
Control for population structure, relatedness, and batch effects.
-
3
Prioritize association peaks with fine-mapping and functional annotation.
-
4
Test causality with perturbation and replication in independent cohorts.
Which statement is most accurate about heritability?
Heritability depends on the population and environmental context in which it is estimated.
Correct answer: It is a property of a trait in a specific population and environment