GeneEnvironment Interaction Virginia Institute for Psychiatric 基因的环境交互作用弗吉尼亚理工大学的精神.ppt

Adding Covariates to Means Model Twin 1 A C E Twin 2 A C E a c e c e a M m+?MM1 M m+?MM2 Matrix Letters as Specified in Mx Script Twin 1 A C E Twin 2 A C E a+?XM1 c+?YM1 e+?ZM1 a+?XM2 c+?YM2 e+?ZM2 M m+?MM1 M m+?MM2 a +aM*D1 c+cM*D1 e+eM*D1 a+aM*D2 e+eM*D2 mu+b*D1 c+cM*D2 mu+b*D2 Main effects and moderating effects Ways to deal with rGE Limit study to moderators that aren’t correlated with outcome Pro: easy Con: not very satisfying Moderator in means model will remove from the covariance genetic effects shared by trait and moderator Pro: Any interaction detected will be moderation of the trait specific genetic effects Con: Will fail to detect GxE interaction if the moderated genetic component is shared by the outcome and moderator Explicitly model rGE using a bivariate framework Pro: explicitly models rGE Con: Power to detect BXU decreases with increasing rGE; difficulty converging AS T aS + βXSM aU + βXUM M aM AU βXS indicates moderation of shared genetic effects BXU indicates moderation of unique genetic effects on trait of interest * * * * * * * * Mediation versus moderation If a variable mediates an effect, significant in the means model, ?M 0 significant increase in a, c or e when ?M is fixed to 0 If a variable moderates an effect ?X0, ?Y0, or ?Z 0 irrespective of ?M or any reduction in a, c or e. * * * * * Mediation versus moderation If a variable mediates an effect, significant in the means model, ?M 0 significant increase in a, c or e when ?M is fixed to 0 If a variable moderates an effect ?X0, ?Y0, or ?Z 0 irrespective of ?M or any reduction in a, c or e. Gene-Environment Interaction Correlation Danielle Dick Tim York VCU workshop, Fall 2010 Gene-Environment Interaction Genetic control of sensitivity to the environment Environmental control of gene expression Bottom line: nature of genetic effects differs among environments Standard Univariate Model P1 P2 A1 A2 C1 C2 E1 E2 1.0 (MZ) / .5 (DZ) 1.0 1.0 1.0 1.0 1.0 1