On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors.: GxE interaction and sibling recurrence risk

Abstract : Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for genetic factors. A test comparing the recurrence risks in sibs according to the exposure of indexes is proposed and its power is studied for varying values of model parameters. The Exposed versus Unexposed Recurrence Analysis (EURECA) is valuable for common diseases with moderate familial aggregation, only when the role of exposure has been clearly outlined. Interestingly, accounting for a sibling correlation for the exposure increases the power of EURECA. An application on a sample ascertained through one index affected with type 2 diabetes is presented where gene-environment interactions involving obesity and physical inactivity are investigated. Association of obesity with type 2 diabetes is clearly evidenced and a potential interaction involving this factor is suggested in Hispanics (P=0.045), whereas a clear gene-environment interaction is evidenced involving physical inactivity only in non-Hispanic whites (P=0.028). The proposed method might be of particular interest before genetic studies to help determine the environmental risk factors that will need to be accounted for to increase the power to detect genetic risk factors and to select the most appropriate samples to genotype.
Liste complète des métadonnées

Littérature citée [20 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00446027
Contributeur : Rémi Kazma <>
Soumis le : lundi 11 janvier 2010 - 17:34:21
Dernière modification le : jeudi 11 janvier 2018 - 06:20:15
Document(s) archivé(s) le : vendredi 18 juin 2010 - 00:42:17

Fichiers

KAZMA_EJHG_2010.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Rémi Kazma, Catherine Bonaïti-Pellié, Jill Norris, Emmanuelle Génin. On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors.: GxE interaction and sibling recurrence risk. Eur J Hum Genet, 2010, 18 (1), pp.88-94. 〈10.1038/ejhg.2009.119〉. 〈inserm-00446027〉

Partager

Métriques

Consultations de la notice

231

Téléchargements de fichiers

99