The presence of a Gene-Environment interaction means that when both factors are detected, the risk is increased compared to the sum (or the multiplication) of each of them.

A first way to use such interaction is to fix a known environmental factor (for example when all patients are being exposed to alcohol) and see how some genes may be involved on related- or endo-phenotypes.

The survival status of a male alcohol-dependent sample (n=126), recruited 9 years before, was for example analysed. We found that the C allele of the 5-HT1b gene, and tobacco dependence, were found in excess in the non-surviving patients, but that no endo-phenotypes are being directly involved.

With this same GxE approach, we also found that a haplotype of the DAT gene was involved in the risk of withdrawal seizures (Le Strat et al., in press) when all patients stopped, at least once in their lifetime, drinking alcohol.

A second strategy is to analyse some environmental factors potentially involved (such as early aggression) and compare these risk factors in patients with or without genetically related vulnerability (such as high initial tolerance to alcohol or familial history of dependence) to explain alcohol abuse or dependence. We will present a new study (S.A.G.E.) based on 3.000 young adults assessed for these factors.

Gene-Environment interactions approach could help to select more accurately specific candidate genes, identify more homogenous subgroups of patients, and ultimately, may lead to more focused, i.e. more efficient, prevention strategies.