heritable and heritability
- The term “heritable” applies to traits that vary in the population and are more similar in parents and offspring than they are in randomly selected individuals in the population.
- The concept of “heritability” was introduced “to quantify the level of predictability of passage of a biologically interesting phenotype from parent to offspring” (Feldman, 151).
heritability and population genetics
\(V_{p} = V_{G} + V_{E} = V_{A} +V_{D} + V_{E}\)
- broad sense heritability, h2b, “the proportion of phenotypic differences due to all sources of genetic variance” (Plomin 1990, 234).
- Narrow sense heritability, h2, “the proportion of phenotypic variance due solely to additive genetic variance” (Plomin 1990, 234).
\(h_{b}^2 = V_{G}/V_{P}\)
\(h^2 = V_{A}/V_{P}\)
measuring heritability: from galton to GWAS
conventional methods don’t rely on genetic data (genetic sequence, snps, etc)
A quantitative framework of family stuides, for example, \(h^2=Vg/Vp ~ covariance(offspring, one parent)\)
More details from Heritability estimation from J.Yang Lab.
genetic data combined with phenotype or endophenotype data
linear mixed model (LMM) framework
y = Xb + Zu + e
X: fixed effect
Z: random effect
u ~ N(0, sigma1)
e ~ N(0, sigma2)
y: phenotype vector
Z: n x p matrix
n: number of samples
p: number of SNPs
element in Z: 0 ,1, 2 <=> aa, Aa, AA
Apply LMM to estimate sigma1 and sigma2
h2 = p*sigma1 / (p*sigma1+sigma2)
if using CpG (or metabolite or gene expression) as endo-phenotype, per CpG site heritability can be estimated.
For example:
In one of my projects, I applied linear mixed model to estimate heritability in fruit fly (Using Drosophila to identify naturally occurring genetic modifiers of Aβ42- and tau-induced toxicity, PMID: 37311212, https://github.com/mingwhy/AD_fly_eye), 02_AD_fly_eye, Caluclate best linear unbiased predictor (BLUP) and broadsense heritability (H2B).
References
- AGRO-932 Biometrical genetics and plant breeding
- AGRO/ANSCI 931 Population Genetics
- Stanford Encyclopedia of Philosophy
- Estimation of variance components and heritability
- 昔时因，今日意 by 杨灿
- Yang, Jian, et al. “Common SNPs explain a large proportion of the heritability for human height.” Nature genetics 42.7 (2010): 565-569.
- Shah, Sonia, et al. “Genetic and environmental exposures constrain epigenetic drift over the human life course.” Genome research 24.11 (2014): 1725-1733.
- Rowlatt, Amy, et al. “The heritability and patterns of DNA methylation in normal human colorectum.” Human molecular genetics 25.12 (2016): 2600-2611.
- Rohde, Palle Duun, Izel Fourie Sørensen, and Peter Sørensen. “qgg: an R package for large-scale quantitative genetic analyses.” Bioinformatics 36.8 (2020): 2614-2615.
- Zhu, Huanhuan, and Xiang Zhou. “Statistical methods for SNP heritability estimation and partition: A review.” Computational and Structural Biotechnology Journal 18 (2020): 1557-1568.