EUROPEAN
RESPIRATORY
JOURNAL
September issue
(Vol. 24, Number 3)
Spin-offs from human genome sequencing:
Respiratory epidemiology
on the brink of a major revolution
writes the European Respiratory Journal (ERJ)
in its September issue.
Deciphering the human genome opens up brand new horizons for
health in general and respiratory disease in particular. Notably, it will
allow a better understanding of the causes and development of
various respiratory conditions whose mechanisms have not yet been
completely elucidated. One important result is that classical
epidemiology - the study of environmental factors conditioning the
appearance, frequency, distribution or development of diseases - will
be increasingly combined with the epidemiology of genetic factors.
According to an article in the September ERJ, which was written by
an international study group specially formed to examine the issue,
and coordinated by Francine Kauffmann of the Epidemiology and
Biostatistics Department at the French National Institute for Health
and Medical Research (INSERM), this revolution represents a major
multi-disciplinary challenge. The article seeks to define the main
directions that might be followed by future research programmes
linking genetic epidemiology to classical epidemiology.
Human genome sequencing, completed in April 2003, is now giving a new boost
to medical research. Both in primary prevention (with the emergence of new
prevention strategies targeted at high-risk populations) and in secondary
prevention, it is raising enormous hopes, as is also the case at the clinical level,
where it should make it possible to offer new treatment options.
Thanks to the knowledge gathered on the human genome, scientists are now
better armed to stop the biological processes in their tracks at the origin of
disease.
But the revolution should be felt especially keenly in epidemiology. As the ERJ
article emphasises, classical epidemiological data are not enough, and there is an
urgent need for strategies that also integrate genetic data into public health
programmes.
One of the challenges of this post-genome period will thus be to provide
adequate training so that epidemiologists with an interest in a particular disease
(or in our case respiratory epidemiologists) are able to draw on all available
data, connected both with the environment and with genetics.
New theories on asthma
This new genetic knowledge should prove particularly useful not only in
understanding how respiratory diseases function, but also in identifying their
causes.
In this field, the authors consider current knowledge to be inadequate: if so
much research has led to inconclusive results, the reason lies largely in the
excessively restricted population samples habitually used in studies.
"Population studies need to be based on large, well characterised samples in
order to study certain sub-varieties of the disease under examination and gain a
better understanding of the interactions among various genes and between genes
and the environment", explains Francine Kauffmann, spokesperson for the ERJ
group on "Post-Genome Respiratory Epidemiology".
The example that springs to mind is that of asthma, a complex disease with
multiple mechanisms that have not been clearly elucidated. Several genes are
involved in the main asthmatic mechanism (allergy), but the condition is also
associated with temporal and geographic variations that have nothing to do with
genetics.
The article's authors feel there is a need to go beyond the hypotheses currently
proposed to explain the global growth in asthma rates, none of which really
seems conclusive. They find that there needs to be rapid development of new
theories on the various causes of asthma and more focused study of the various
sub-types, of this particularly complex condition.
The same needs to be done for COPD, especially chronic bronchitis and
emphysema. While it is certainly evident that smoking is the number one risk
factor, it is no less clear that genetic factors play a role. Here again, there is an
urgent need to establish the roles of the genes already discovered and identify
new ones.
Difficult marriage
The road ahead will still be a difficult one, with numerous obstacles and major
challenges, the authors warn.
On the purely practical level, the marriage between classical and genetic
epidemiology will only be able to produce useful results if certain very specific
conditions can be met. Future studies, for example, "should not only
systematically gather the genetic profiles of participants; they should also be
designed for adaptability to new developments in genetics", Kauffmann
emphasises.
Therefore, new standards and new recruitment methods will have to be defined.
The development of Networks of Excellence at the international level, and
especially at the European level, could pave the way for new multidisciplinary
research programmes.
The most delicate issue, however, is bound to be ethics.
Scientists are increasingly interested in heterogeneous populations rather than
the high-risk individuals they have focussed on up to now, therefore the very
notion of ethics will need to evolve.
"Most ethics codes have concentrated on individual rights (autonomy, consent,
discrimination, confidentiality, etc.). The guidelines proposed no longer
completely respond to the new issues raised by population banking studies. The
development of normative frameworks appears necessary", the authors write.
The post-genome period is certainly very promising, but there are immense
challenges on the way to a better and more modern epidemiology.