FREQUENTLY ASKED QUESTIONS
Where does the study’s name come from? Or Why have we called
this the CHANGE study?
It stands for “Congenital Hearts – A National Gene/Environment Study”.
So it is a national study intended to find out about both inherited factors
(genes) and factors related to the environment in which people live that are
important in the causation of Congenital Heart Disease.
What is congenital heart disease?
Congenital heart disease is the name given to a group of conditions in which
a baby is born with some type of malformation of his or her heart. Overall,
7 in 1000 newborns have some form of congenital heart disease. Many of these
cases are mild and some resolve on their own as a child grows, but a significant
proportion are severe and may require corrective heart surgery in early life.
The CHANGE study is looking at a particular type of congenital heart disease
known as Tetralogy of Fallot, which is one of the most common severe congenital
heart conditions, and children with this condition often require surgery within
the first year of life.
Why are you studying genes for congenital heart disease?
We know that there are some forms of congenital heart disease which are very
strongly influenced by an individual’s genetic makeup. For example, babies
with Down’s syndrome, in which there is one extra copy of a large number
of genes in every cell in the body, are very likely to have congenital heart
disease. There are many other similar, individually rare, syndromes which involve
congenital heart disease. There are also a very few families in which congenital
heart disease is present because of just one faulty gene. But if we add all
these together we are only able to explain the cause of about 20% of the cases
of congenital heart disease. The remaining 80% of cases occur because of a complex
interplay between inherited factors and the early environment.
Why are you studying Tetralogy of Fallot?
There are several ways one could go about trying to work out the genetic changes
that contribute to congenital heart disease. One could group all types of congenital
heart disease together but it is likely that that the genes important in one
type of congenital heart disease will be less important in another type even
if there is some overlap. We think it gives us a better chance of identifying
the important factors if we start with a group of people who all have the same
condition. Dr Farrell (the statistician in the team) worked out we need approximately
a thousand cases to identify the genetic changes important for a particular
heart defect. We chose to start with Tetralogy of Fallot because it is an important
condition and it is common enough that it is feasible to collect a thousand
cases.
If we are successful in identifying the genetic factors contributing to Tetralogy
of Fallot it demonstrates this approach works and we can extend our studies
to other types of congenital heart defect and test whether the factors contributing
to Tetralogy of Fallot are important in other congenital heart defects.
What is Tetralogy of Fallot
Please click here for an explanation of Tetralogy of Fallot provided by the British Heart Foundation.
What is your approach?
We are collecting “trio” families consisting of a person with Tetralogy
of Fallot and both his/her parents, although we understand this is not always
possible and we would still be very grateful for volunteers even if both parents
were not able to participate. The age of the affected person does not affect
their eligibility to participate in the study. After fully explaining the study,
and being certain that the family have given us their fully informed consent
to go ahead, we record some details about the family members and their medical
histories at an interview. Participation in the study is voluntary and all personal
details are kept confidential so samples and questionnaires are anonymised.
We obtain a blood sample from all three members of the family (where people
are just too afraid of needles to give a blood sample, as sometimes happens,
we can take a sample of saliva instead though this limits what we are able to
study in the laboratory). We extract the genetic material (which is called DNA)
from the donated sample and we look for changes in particular genes that are
needed to make a normal heart. We are looking for two types of changes: those
that will definitely prevent that genetic instruction from working and variants
that may affect how a gene works. Congenital heart disease may be caused by
a major change in just one gene or a combination of minor changes in a number
of genes. Our approach to work out if a minor change address does influence
heart formation is to look at its frequency in a large number of people with
congenital heart disease, its frequency in the parents and whether it is passed
on to children with congenital heart disease more often than one would expect
by chance. At present, we are looking at a panel of 50 genes which have been
suggested to be of importance in determining the risk of congenital heart disease.
Because the early environment that the baby is exposed to in the womb may also be very important in determining risk of congenital heart disease, we are also collecting samples from volunteer women who have not had a child with congenital heart disease so we can see whether there are any differences in genes which could affect the early environment between those women who have had a child with Tetralogy of Fallot and those women who have not.
If my family takes part will we get results?
Neither you nor your doctor will get individual results. The samples are anonymised
before they reach the laboratory.
If the research finds that changes in a particular gene do contribute to some
cases of Tetralogy of Fallot then tests for that gene can be developed in a
diagnostic laboratory and could be offered to you by your cardiologist. You
would then have information on what is being tested and how long it would take
to get a result if you decided to proceed.
