Analysis of Gene-Environment Interactions in Alzheimer's Disease

 
   Lead Investigator:    Iryna Lobach
   Institution      :    UCSF
   E-Mail           :    Iryna.Lobach@ucsf.edu
   Proposal ID      :    149



   Proposal Description:
   The complex diseases, such as Alzheimer's, are jointly influenced by multiple                                                                                     markers with potential interactions. Therefore, it is more intuitive to view      the underlying genetic model as one multivariate model, instead of a group of     single-marker models. Our assumptions for the underlying genetic models are       more in line with the view of considering joint effects and interactions,         instead of the oversimplified single-marker model. In our project we will         perform a novel pathway analysis which offers the opportunity to combine          association evidence from multiple genetic variants and thus potentially has a    better chance of identifying the association between the pathway and the          disease.                                                                                                                                                            Presence of dependence between the genetic and environmental factors poses a      challenge in the traditional analysis of gene-environment interactions.  We       propose a novel methodology for analysis of data in the presence of complex       gene-environment interactions, consisting two major parts. First, we              characterize the relevant dependence structure between genetic and                environmental factors, (in the case of Alzheimer's, diplotype effects and       medical conditions). Second, we incorporate the dependence structure into the     regression analysis.                                                              We propose to pursue the following aims:                                          Aim 1: Develop and apply a novel methodology for modeling and analysis of the     ADGC data to examine the relationship between multiple genetic factors and risk                                                                                     of developing Alzheimer's Disease