Heritability

The concept of heritability recognizes that traits are a product of both genetic and non-genetic (referred to as environmental) effects. Some phenotypes (like cystic fibrosis) are predominantly influenced by alleles at one or a few genes and are most usefully thought of in terms of the discrete effects of classical Mendelian genetics. However, other phenotypes (like stature) fall at the opposite end of the scale and are influenced by many small effects of variation at many genes and well as significant environmental effects and are addressed in a collective approach. (While many phenotypes fall intermediate on this scale and may have a few genes of large effect and many genes of smaller effects along with environmental/non-genetic influences.)

When speaking about heritability of complex traits we often do not know precisely which or how many genes are involved. However, this does not mean that we cannot be precise and quantitative in understand and predicting the genetic influence on the trait. Many traits have a significant heritable/genetic component even if the genetic variants involved are unknown and diffuse (spread out over many loci). The field of quantitative genetics, of which heritability is a part, is necessarily very statistical in nature.

Many phenotypes vary over a range of measurement. The variance of the phenotype can be estimated. Both genetic variation and environmental variation contribute to phenotype variance. If genetic effects and environmental effects are independent of each other (which is a natural place to start) then the total variance of the phenotype (V_T) is the sum of the individual genetic (V_G) and environmental (V_E) variances.

[math]V_T = V_G + V_E[/math]

Broad sense heritability (H²) is the proportion of variation in a phenotype that is due to genetic variation.

[math]H^2 = \frac{V_G}{V_T}[/math]

In brief, comparisons of the phenotypes of groups of individuals that are genetically identical (and differ only in chance environmental effects) versus individuals that are genetically diverse (and differ in both genotypes and environment) allow H² to be estimated.

However, in some cases it is easier and/or more useful to estimate narrow sense heritability (h²). This is the fraction of variation in a phenotype that is due to additive genetic effects. Genetic effects on phenotypic variation can be broken down into additive effects (V_A), effects due to dominance (V_D), and the variance due to epistatic interactions (V_I).

[math]V_G = V_A + V_D + V_I[/math]

[math]h^2 = \frac{V_A}{V_T}[/math]

Additive genetic effects are similar to the pattern of incomplete dominance where heterozygotes are intermediate between homozygotes in a phenotype. However, this is carried a step further so that alleles that contribute towards a particular direction in phenotype are additive both within and between genes.

Linear regression was developed to estimate narrow sense heritability by comparing parents and offspring. Narrow sense heritability also predicts the response to artificial selection in the breeder's equation,

[math]R = h^2 S[/math]

where S is the degree of selection and R is the response to selection in the average phenotype among offspring.

Because environmental effects (access to resources, shared cultural differences, exposure to certain environmental variables) and genetic variation are correlated between parents and offspring it can be very difficult to estimate heritability in humans for certain traits (and in such cases heritability tends to be overestimated). However, studies of identical versus non-identical twins and siblings that were adopted at birth into different families versus reared together have been used to try to address this. Regardless heritability patterns in humans can be complex and additional factors such as Socioeconomic Status may need to be taken into account Turkheimer et al. 2003.

Natural selection and heritability interact. Traits that strongly influence relative fitness such as those closely connected to reproduction (litter size, time until weaning, etc.) tend to have low heritability because V_G is minimized relative to V_T (Mousseau and Roff 1987)

With sufficient data (dense genotypes across the genome and large sample sizes) the genetic loci underlying complex traits can be identified; however, fully mapping the heritable components of a trait on a gene by gene level can be very challenging (Yang et al. 2011; Shen 2013).

Links

Review: Visscher et al. 2008