Examination of the Effect of Rare Variants in TREM2, ABI3, and PLCG2 in LOAD Through Multiple Phenotypes
| Autor: | Anne M. Fagan, John P. Budde, Oscar Harari, Jorge L. Del-Aguila, Kristy Bergmann, Jen Gentsch, Fabiana H.G. Farias, Joanne Norton, Umber Dube, Zeran Li, Joseph Bradley, John C. Morris, Maria Victoria Fernandez, Fengxian Wang, Beau M. Ances, Carlos Cruchaga, Claudia Olive, Laura Ibanez, Bruno A. Benitez |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Candidate gene Amyloid Late onset Disease Article Cohort Studies 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Internal medicine Databases Genetic medicine Humans Receptors Immunologic Adaptor Proteins Signal Transducing Aged Aged 80 and over Membrane Glycoproteins Phospholipase C gamma TREM2 business.industry General Neuroscience Genetic Variation General Medicine Phenotype Psychiatry and Mental health Clinical Psychology 030104 developmental biology Endophenotype Cohort Female Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | J Alzheimers Dis |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Background: Rare variants in PLCG2 (p.P522R), ABI3 (p.S209F), and TREM2 (p.R47H, p.R62H) have been associated with late onset Alzheimer’s disease (LOAD) risk in Caucasians. After the initial report, several studies have found positive results in cohorts of different ethnic background and with different phenotype. Objective: In this study, we aim to evaluate the association of rare coding variants in PLCG2, ABI3, and TREM2 with LOAD risk and their effect at different time points of the disease. Methods: We used a European American cohort to assess the association of the variants prior onset (using CSF Aβ42, tau, and pTau levels, and amyloid imaging as endophenotypes) and after onset (measured as rate of memory decline). Results: We confirm the association with LOAD risk of TREM2 p.R47H, p.R62H and ABI3 p.S209F variants, and the protective effect of PLCG2 p.P522R. In addition, ABI3 and TREM2 gene-sets showed significant association with LOAD risk. TREM2 p.R47H and PLCG2 p.P522R variants were also statistically associated with increase of amyloid imaging and AD progression, respectively. We did not observe any association of ABI3 p.S209F with any of the other AD endophenotypes. Conclusion: The results of this study highlight the importance of including biomarkers and alternative phenotypes to better understand the role of novel candidate genes with the disease. |
| Databáze: | OpenAIRE |
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