JI award: Polygenetic risk score for AD

 
   Lead Investigator:    Rahul Desikan
   Institution      :    U California, San Francisco
   E-Mail           :    rahuldesikan@gmail.com
   Proposal ID      :    722


   Publications:


1  Desikan RS, Fan CC, Wang Y, Schork AJ, Cabral HJ, Cupples LA, Thompson WK,  Besser L, Kukull WA , Holland D, Chen C, Brewer JB, Karow DS, Kauppi K, Witoelar A, Karch CM, Bonham LW, Yokoyama JS, Rosen HJ, Miller BL, Dillon WP, Wilson DM, Hess CP, Pericak-Vance M, Haines JL, Farrer LA, Mayeux R, Hardy J, Goate AM, Hyman BT, Schellenberg GD, McEvoy LK, Andreassen OA, Dale AM
   Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score
   Journal Article  PLoS Med,14:e1002258,2017,PMC5360219

   PUBLISHED



2  Tan CH, Bonham LW, Fan CC, Mormino EC, Sugrue LP, Broce IJ, Hess CP, Yokoyama JS, Rabinovici GD, Miller BL, Yaffe K, Schellenberg GD, Kauppi K, Holland D, McEvoy LK,   Kukull WA  , Tosun D, Weiner MW, Sperling RA, Bennett DA, Hyman BT, Andreassen OA, Dale AM, Desikan RS
   Polygenic hazard score, amyloid deposition and Alzheimer's neurodegeneration
   Journal Article  Brain,142:460-470,2019,PMC6351776

   PUBLISHED



3  Tan CH, Hyman BT, Tan JJX, Hess CP, Dillon WP, Schellenberg GD,  Besser LM, Kukull WA , Kauppi K, McEvoy LK, Andreassen OA, Dale AM, Fan CC, Desikan RS
   Polygenic hazard scores in preclinical Alzheimer disease
   Journal Article  Ann Neurol,82:484-488,2017,PMC5758043

   PUBLISHED





   Proposal Description:
   Aim 1:  Determine whether our polygenic hazard score predicts the time to progress to AD. Using clinical and cognitive data from the NACC and a survival analysis framework, we will evaluate whether our recently validated polygenic hazard score predicts the time to progress from normal aging (CDR = 0) and mild cognitive impairment (MCI) (CDR = 0.5) to clinical AD (CDR #8805 1.0). Using neuropathology variables from the NACC, we will validate these findings in a subset of individuals meeting neuropathological criteria for AD.  Aim 2: Evaluate whether a combination of genetic, clinical, cardiovascular and cognitive variables can be integrated into a multidimensional AD prediction score. We will determine whether genetic, cardiovascular, clinical and neuropsychological variables from the NACC can be combined into a prediction score to quantify the risk associated with developing clinical AD. Using a large independent dataset of older controls, MCI and AD participants from Norway, we will validate this multidimensional risk score.  We expect that our polygenic risk score will identify nondemented older individuals at greatest risk for AD and that a combination of genetic, clinical and cognitive variables will provide a powerful method for predicting age-associated AD onset.