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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
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National Institute on Aging
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Cruchaga, Carlos; Karch, Celeste M; Jin, Sheng Chih et al. (2014) Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease. Nature 505:550-4
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
Guerreiro, Rita; Bras, Jose; Hardy, John et al. (2014) Next generation sequencing techniques in neurological diseases: redefining clinical and molecular associations. Hum Mol Genet 23:R47-R53
Thambisetty, Madhav; Beason-Held, Lori L; An, Yang et al. (2013) Alzheimer risk variant CLU and brain function during aging. Biol Psychiatry 73:399-405
Guerreiro, Rita Joao; Baquero, Miquel; Blesa, Rafael et al. (2010) Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging 31:725-31
Nalls, M A; Guerreiro, R J; Simon-Sanchez, J et al. (2009) Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer's disease. Neurogenetics 10:183-90
Peuralinna, Terhi; Oinas, Minna; Polvikoski, Tuomo et al. (2008) Neurofibrillary tau pathology modulated by genetic variation of alpha-synuclein. Ann Neurol 64:348-52
Clarimon, J; Djaldetti, R; Lleo, A et al. (2008) Whole genome analysis in a consanguineous family with early onset Alzheimer's disease. Neurobiol Aging :