Biology Reference
In-Depth Information
heritability is readily estimated by decomposing the phenotypic covari-
ance between pairs of individuals based on their kinship:
Covði; jÞ¼2f
ij
s
g
Covði; iÞ¼s
g
þ s
e
(12.1)
h
2
¼ s
g
=s
P
where Cov(i, j) is the covariance between different individuals i and j, and
Cov(i, i) represents the variance for the ith individual,
f
ij
is the kinship
g
e
coefficient between i and j,
s
is the additive genetic variance,
s
is the
P
is the total pheno-
error (sometimes termed environmental) variance,
s
e
, and h
2
is the additive
genetic heritability which measures the relative contribution of additive
genetic factors to the overall observed phenotypic variance. Twice the
“kinship” coefficient in this context refers to the expected proportion of
alleles shared identical by descent (IBD) by two individuals given their
degree of relatedness: siblings share half their alleles IBD, half-siblings
one-fourth of their alleles, and so on. Alleles shared IBD are necessarily
also identical by state (IBS), a distinction that we discuss in more detail
below. The genetic variance is a cumulative variance; it represents the
summation over all additive genetic factors for the phenotype. Hence,
depending upon the phenotype, it may represent the influence of a single
genetic variant or that of many hundreds of genetic variants.
If variation in a phenotype were due entirely to genetic causes (and
these could be clearly discerned) the heritability of the trait would be 1.
Due to multifactorial causation and measurement error, a typical range of
heritability for many quantitative traits is 30
P
¼ s
g
þ s
typic variance of the trait given by
s
80% of total variance, and
estimates may differ widely from one study to another due to sampling
error. The heritability is a critical measure of the importance of within-
population genetic variation. This single metric conveys whether or not
the search for the individual contributing genes is merited for a given
phenotype.
e
FUNCTIONAL GENETIC VARIATION IS THE
SOURCE OF HERITABILITY
What is the biological source of heritability in humans? Ultimately, it
comes from observable functional genetic variation at the sequence level.
A functional variant is one that influences the focal phenotype via some
molecular mechanism. Thus, functional variants can be considered to be
phenotype specific in this context. If the variant influences a quantitative
