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Génétique épidémiologique de la schizophrénie. Données récentes et stratégies de recherche

Published online by Cambridge University Press:  28 April 2020

D. Campion*
Affiliation:
Centre Hospitalier Spécialisé du Rouvray, 76301Sotteville-les-Rouen, France
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Résumé

Les études épidemiologiques ont mis en évidence une agrégation familiale de la schizophrénie et ont permis de préciser l’étendue du spectre (cf. Tableaux I et II).

Cependant, ces résultats n’impliquent pas automatiquement l’existence d’une composante génétique dans le déterminisme de la maladie. Pour établir la présence de cette composante, on utilise les analyses de ségrégation, de linkage et d’association. Les études de ségrégation, bien qu’elles souffrent de nombreuses limitations, sont plutôt en faveur d’une transmission polygénique avec effet de seuil. Les études de linkage utilisant la méthode des Lod Scores sont encore rares et, comme dans toutes les maladies oú le mode de transmission n’est pas connu, leur emploi pose des problémes méthodologiques complexes. Il semble toutefois que si la détermination de la distance entre le géne pathologique et le marqueur utilisé est sensible á des erreurs sur les paramétres caractérisant le locus de susceptibilité, on ne puisse conclure á un faux linkage á partir de données erronées. Pour effectuer un test de linkage, on peut également employer la méthode des germains malades (Affected Sib Pair), qui, bien que moins puissante, offre des avantages lorsque le mode de transmission de la maladie est mal connu. Enfin, l’interêt d’une étude d’association en utilisant des polymorphismes de restriction au voisinage de génes candidats est souligné. De toute évidence, ces différentes approches devront être combinées dans la recherche des facteurs génétiques prédisposant á la schizophrénie.

Summary

Summary

Epidemiologic studies have shown a familial aggregation of schizophrenia and have allowed to clarify the relationship between schizophrenia and other psychiatric disorders. However, these results are not automatically involving a genetic componment in the disease's etiology. Segregation's analysis are affected by many shortcomings, but the multifactorial polygenic threshold model as mode of inheritance has received the most support. The linkage studies with the Lod score method are still scarce and in all the diseases where the mode of inheritance is unknown, their use raise many methodological problems. It seems that the estimation of the recombination fraction may be strongly affected by an error on any genetic parameter at the disease's locus, but despite these errors, the test himself remains robust. Another way to perform a linkage test is the use of the affected sib pair method, which does not rely on questionable assumptions about the mode of inheritance of the disease.

Association studies, using RFLP near candidate genes are an interesting approach. In fact all these methods should be combined in the search of genetic factors.

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Revue
Copyright
Copyright © European Psychiatric Association 1989

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