Biomedical Engineering Reference
In-Depth Information
relatives of cases compared with the relatives of controls (i.e., individuals
without respiratory disease) (4-8). This increased prevalence could not be
explained by factors such as age, sex, and smoking history. In addition,
the prevalence of COPD and the correlation of lung function have been
shown to decrease with increased genetic distance (e.g., in second degree
relatives vs. first degree relatives) (9,10). In the general population unse-
lected for airflow limitation, there was a higher correlation of lung function
between parents and their children or between two siblings than between
spouses (11,12).
B. Twin Studies
Twin studies provide a means to estimate the relative contributions of genes
and environment to a trait, by comparing the correlation of the trait in
monozygotic (MZ) twins with the correlation in dizygotic (DZ) twins.
Webster et al. (13) studied 45 pairs of apparently healthy MZ twins,
comparing maximum expiratory flow at 60% of total lung capacity in smo-
kers and nonsmokers, and found that this test could discriminate smokers
from nonsmokers, among pairs of twins in which one member smoked
and the other did not. The intra-pair difference of this test in pairs where
both members smoked was the same as in pairs in which both members
did not smoke, supporting the view that genetic factors are important in
determining the vulnerability of the airways to cigarette smoke.
Studies of twins raised together may reflect the similar childhood
environments as much as the genetic make-up of the twins. In order to over-
come this problem, Hankins et al. (14) studied 15 pairs of MZ twins and one
set of MZ triplets, who were separated soon after birth and raised apart. Six
twin pairs were concordant for nonsmoking and six were discordant. Three
pairs and the triplets were concordant for smoking. The results of this study,
along with those of the previous studies of twins raised together, support the
conclusion that genetic factors are important in determining susceptibility to
COPD due to chronic cigarette smoke exposure.
The proportion of the variability of a trait due to genetic factors is
known as the heritability of that trait, and for forced expiratory volume
in one second (FEV
1
), this proportion ranges from 50-80% (15,16). Varia-
tion in heritability estimates in these studies could be due to differences in
exposure to environmental factors and
=
or differences in genetic make-up
of the respective populations.
C.
Segregation Analyses
Although twin studies provide evidence for a genetic basis to a disease, they
are unable to identify the nature or number of inherited factors involved. In
order to achieve this, a technique known as segregation analysis can be
