Strategies to study lifestyle and genetic factors related to chronic
13 December 2011
A group of scientists has examined the challenges associated
with chronic inflammatory diseases, and described 10 key areas with the
highest priority for research, in a study under the auspices of
the European Science Foundation (ESF).
Their recommendations are published in a supplement to The
Journal of Allergy and Clinical Immunology (JACI), the official
journal of the American Academy of Allergy, Asthma & Immunology
A dramatic increase in the incidence of chronic inflammatory
diseases such as asthma, allergy, and irritable bowel syndrome, has
led to concern about how modern lifestyles may trigger physiological
“Many transmissible diseases have been effectively eradicated
over the last half century, yet there has been a marked increase in
the incidence of chronic inflammatory diseases,” says committee
chair Harald Renz, MD, of the Institute of Laboratory Medicine and
Pathobiochemistry, Molecular Diagnostics, Phillips University,
Marburg, Germany. Strategies are urgently needed to determine the
causes of these chronic diseases and identify targets for therapy
Factors responsible for the development of chronic inflammatory
diseases are not easily determined. While epidemiological evidence
clearly points to an environmental influence, not all individuals in
these environments develop disease. Susceptibility to chronic
inflammatory disease has a clear genetic component, but genetics may
not be the only determining factor. Prenatal exposures can influence
later susceptibility to disease. After birth, factors such as
breastfeeding and exposure to microorganisms appear to further
influence the likelihood of developing diseases such as asthma and
Dr. Renz and his colleagues on the Scientific Committee of the
ESF Forward Look on Gene-Environment Interaction in Chronic Disease
(GENESIS) identified the following 10 key recommendations as having
the highest priority for research into chronic inflammatory
- Research should distinguish between therapy and prevention.
- Large prospective cohort studies including deep phenotyping
should be made a priority.
- Research should focus on the question of tolerance.
- A global (international) approach should be taken to
understanding chronic inflammatory disease.
- Effective interdisciplinary research strategies must be
- New tools and experimental models must be developed.
- Protocols for data collection, handling, and storage need to
- Substantial investment must be made in infrastructure,
personnel, and development of research tools.
- Dedicated funding must be provided for interdisciplinary
- Effective public-private partnerships must be developed to
ensure free exchange of information.
Furthermore, the committee pointed to a series of key strategic
research targets for which significant progress in the management of
chronic diseases may be achieved.
Therapy and Prevention. Given the complexity of chronic
inflammatory diseases, therapies must be based on deep
environmental, clinical and biological phenotyping of patients.
Without deep phenotyping, it is impossible to determine whether a
potential therapy is clinically ineffective or simply
inappropriately targeted. The committee calls for the identification
of novel biological markers to enhance patient stratification, and
for investments in bioinformatics and systems biology to realize the
full potential of omics data.
For prevention, key issues include the selection of appropriate
populations and the long-term tolerability of putative long-term
protective agents. The results of clinical studies of probiotics as
infant food supplements to prevent allergic disease have been mixed.
The committee recommends that the term probiotic be employed with
caution, and that further research be done to understand the
function of gut microbes in health and disease.
Large Cohort Studies. The committee calls for large cohort
studies, initiated prior to birth, to fully take into account the
impact of how intrinsic and extrinsic factors determine the
probability that an individual will be healthy or develop a chronic
disease, given the right environmental stimuli. Such studies would
analyze biological data including genomic, clinical, and
environmental factors, and also psychosocial factors such as stress.
It will be important to ensure international collaboration and
coverage of populations with different lifestyles and environmental
Partnerships. The shifting global pattern of chronic disease to
developing nations offers an opportunity to identify key factors
that confer both risk and protection. The committee recommends that
research projects be established in regions with low or developing
risk of chronic inflammatory disease, and the establishment of
parallel birth cohorts in low- and high-risk regions.
Cross-disciplinary partnerships will be essential as well,
extending beyond traditional disciplines such as epidemiology and
microbiology to mathematics, virology, and ecology. Finally,
effective private-public partnerships, with more fluid exchanges of
information between academia and industry, will be a key driving
force for future research.
Research Tools, Data Generation and Management, and
Infrastructure and Personnel. New research strategies that consider
the diversity of the microbiome in the choice of experimental models
and the potential reproducibility of results will be needed. Because
of the complexity introduced by the microbiome, substantial
investment will be required to develop the bioinformatics and
systems biology approaches required to analyze the datasets
n electronic infrastructure to support integrated approaches and
open collaboration will be necessary. Funding should be made by
panels in which no specific discipline is over-represented to
support unbiased approaches. And, a new generation of biological and
medical scientists will need to be ready to exploit rapid
developments in information technology. They will need to use
insights from a range of scientific disciplines as well as fields as
diverse as finance and engineering. The committee suggests the
creation of international graduate schools to provide specific
training in interdisciplinary research.
In the foreword accompanying the supplement, Lars V. Kristiansen,
PhD, Science Officer, European Science Foundation, European Medical
Research Councils, Strasbourg, France, and colleagues comment, “The
socioeconomic costs of chronic diseases are staggering and ever
increasing. There is an urgent need to prioritize resources and
identify the most efficient scientific and societal initiatives to
be adopted. National collaboration within the European region
represents the most efficient manner in which strategies for
amelioration of chronic inflammatory diseases in the western world
may be achieved.”
The supplement is entitled “Gene-Environment Interaction in
Chronic Disease – An ESF Forward Look,” by H. Renz, I.B. Autenrieth,
P. Brandtzaeg, W.O. Cookson, S. Holgate, E. von Mutius, R. Valenta,
and D. Haller. It appears as The Journal of Allergy and Clinical
Immunology, Volume 128, Supplement (December 2011) published by
The supplement is freely available through the JACI website at