Clustering of phenotypes and correlations with genotypes

 
   Lead Investigator:    Debby Tsuang
   Institution      :    University of Washington
   E-Mail           :    dwt1@u.washington.edu
   Proposal ID      :    559



   Proposal Description:
   Aim 1 is to uncover the genetic architecture of complex genetic disorders, such as Alzheimer???s disease, we propose to determine how clusters of demographic and clinical variables may be associated with genetic risk factors.     Aim 1a. Include all NACC subjects with diagnosis of probable AD and controls with normal cognition at baseline who have undergone GWAS as part of ADGC.   Aim 1b. deconstruct the AD phenotype independently of the genotypes to determine how many cluster patterns exist (see below) within AD and both AD and controls. We will utilize demographic, clinical and neuropsychological variables to differentiate within cases.  We will conduct similar analyses for controls.     In aim 2 we will review genes listed in the websites such as http://www.ebi.ac.uk/gwas/ to assemble a set of genes and/or SNPs that account for a high variance for late-onset AD. We will set the variance accounted for from 30 to 60. We will derive a composite genetic score from this list of genes and/or SNPs for each NACC subject. Subsequently, we will conduct a joint phenotype-genotype correlation analyses based on the phenotype clusters (separately for both cases and controls) derived in Aim 1b.