FL "Gene Environment Interaction in Chronic Disease" (GENESIS)

Forward Look Meetings

Three strategic workshops took place in Barcelona in late October 2010:
Workshop 1: Intrinsic mechanisms in chronic disease
Workshop 2: Extrinsic mechanism in chronic disease
Workshop 3: Therapy and Prevention - Emerging Concepts

A final Consensus Conference was held in Berlin on 15-16 March 2011.

More information on these events can be found at the List of Activities page.

Forward Look Background

Over the last few decades a dramatic increase in Chronic Inflammatory Diseases is being observed, particularly within the industrialized world. Clinical manifestations at the mucosal surfaces of the airways and the gastrointestinal tract are of major importance in this regard. Model diseases comprise bronchial asthma, allergic rhinitis and chronic inflammatory bowel disease. Clinical phenotypes are characterized by an inappropriate immune response. In the case of allergic and chronic inflammatory diseases, an inflammatory response against harmless environmental antigens is formed; in autoimmunity the immune system reacts against harmless self antigens.

These diseases have a tremendous socio-economic impact. Worldwide about 300 million people are suffering from asthma according to the most recent ISAAC-study. A cost-of-illness study by the Joint Research Centre (JRC) of the European Commission has estimated the total burden of asthma in children under the age of 15 in the 25 EU member states to be €3.0 billion each year. The total burden of asthma to the European community is at least double when taking adult and occupational asthma into account. Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are spontaneously relapsing, immune-mediated disorders of the intestinal tract. Both disorders affect females and males, children and adults, with a combined frequency of 5-200 cases per 100,000 Europeans. The frequency of IBD has increased in recent decades and will likely increase particularly in countries of economic transition. With a peak age of onset in adolescence or early adulthood, IBD has the potential to cause 60-70 years of suffering in individual patients, with a significant impact on quality of life and work absenteeism.

Although it is now well accepted that the immunological dysregulation is a result of a complex gene-environment interaction the detailed nature of this dysregulation remains to be characterized on the cellular and molecular level. Over the last few years multiple disease susceptibility genes have been identified. However, the functional consequences in terms of altered signalling pathways remain to be identified. Furthermore, the level of gene-gene-interaction opens a new area of future research.

Based on the genetic disposition, environmental factors determine phenotype development to a large extent. Recent research indicates that altered lifestyle conditions including nutrition and exercise play an important role in this regard. Furthermore, the hygiene hypothesis provides a challenging concept for the explanation of increases in chronic inflammatory diseases. In this regard the complex gut-associated microbial ecosystem (gut-microbiota) and nutrition-related factors are the most important environmental triggers for the development and modification of lifestyle-related diseases, including metabolic pathologies. The coexistence of the host with its intestinal microbiota is tightly controlled at various levels and an accumulating body of evidence suggests that the failure of this homeostasis is an important contribution to disease development. Furthermore, the intestinal microbiota affects the storage and the development of type-2 diabetes through gut- and liver-derived mechanism linking bacterial signals with altered lipid metabolism. Recent evidence indicates that this gut- and metabolic-associated diseases share common traits in their cellular pathogenesis, suggesting a link between inflammatory processes and metabolic signalling pathways.

The European Medical Research Councils have identified this area as an important topic to address at the European level and have decided to launch a new foresight initiative entitled ‘Gene Environment Interactions in Chronic Disease’.

Forward Look Objectives

The vision of this Forward Look is to achieve, by means of a concerted strategy between with medium and long term perspectives, a breakthrough in causative and efficacious treatment and prevention strategies for chronic inflammatory diseases at surfaces. Specifically through international workshops between scientific communities, industries, patient organisations and policy makers, the activity aims at developing an agenda for a genetically based and pathogenicity driven research program that will reveal novel concepts for diagnostics, primary prevention and treatment of allergies at the respiratory tract such as asthma as well as inflammatory bowel disease including Crohn´s disease and ulcerative colitis.

In conclusion, this Forward Look aims at identifying patients with host genetic factors, microbiome and environmental factors predisposing for chronic inflammatory diseases at the respiratory and gastrointestinal tract. Gene environment analyses will provide the basis for development of early causative treatment by modifying pathogenic pathways or will by developing biomarkers allowing the identification of subjects at risk that may benefit from rational primary and secondary prevention strategies. It will have a highly positive impact on the society with better patient treatment and therapies.

ESF Forward Looks

ESF Forward Looks provide medium- to long-term authoritative visions on science perspectives in broad areas of research bringing together ESF Member Organisations, other research organisations and the scientific community in creative interaction. Forward Look reports and other outputs such as ESF Science Policy Briefings assist policy makers and researchers in defining optimal research agendas and in setting priorities. Quality assurance mechanisms, based on peer-review where appropriate, are applied at every stage of the development and delivery of a Forward Look to ensure its credibility and impact.