We continue to be a contributor to the reanalysis of large tracts of genome wide association data and much of this work, which identifies several new loci, and a converging molecular pathway, has been published. We have expanded this work to characterize the extent of genetic variability at the CLU and PICALM loci, and to examine the role of variants in these and other loci as quantitative trait loci. In this respect our efforts have used the reference data generated within our laboratory that facilitates testing association between candidate variants and gene expression and/or proximal DNA methylation. In addition, we are currently working with collaborators at UCL to perform exome sequencing on families and individuals with Alzheimer's disease;this work aims to identify moderate- to high-risk variants associated with disease. Most recently our efforts using second generation sequencing have lead to the identification of TREM2 variants as a risk factor for Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000950-12
Application #
8736664
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2013
Total Cost
$438,510
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
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Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael et al. (2014) Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease. Neurobiol Aging :
Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael et al. (2014) Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiol Aging 35:2422.e13-6
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