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Genetic risk and gene-environment interaction in complex diseases: a network-based causality?| old_uid | 9892 |
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| title | Genetic risk and gene-environment interaction in complex diseases: a network-based causality? |
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| start_date | 2011/04/29 |
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| schedule | 14h |
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| online | no |
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| details | Sa présentation sera suivie par un commentaire d'Anouk Barberousse (IHPST, Paris) |
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| summary | Complex diseases show both a genetic component and a response to environmental factors and lifestyle changes. Since a few years, genome-wide association
studies have succeeded in identifying hundreds of genetic polymorphisms associated with a stronger risk to complex diseases. However, association is weak and none of the variant forms of the genetic loci are either necessary or sufficient to develop the disease.
We promote a network view of the biological function affected in the disease, centered on robustness and redundancy: as long as one functional path remains, the function is ensured. To get quantitative insights, we adapt reliability theory to complex diseases networks. In our view, genetic factors reduce the initial number of available paths, while environment, contingent surroundings, personal history, epigenetics and intrinsic stochasticity influence their persistence time. Our model allows to reproduce age-related incidence curves and understand the influence of environmental changes.
Complex diseases thus question the standard notion of causality, replaced by a network of causal relationships with a strong influence of historical or contingent factors. In short, genetic risk is definitely a risk. Accordingly, genome profiling has little use at the individual level, but it could be useful at population level in devising global models to guide decisions in health care policy.
Joint work with Gaëlle Debret and Jean-Marc Victor (LPTMC, Paris), Leigh Pascoe (CEPH, Paris), Camille Jung and Jean-Pierre Hugot (Hôpital Robert Debré, Paris) |
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| responsibles | Kostyrka, Laplane |
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