Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer's Disease Sequencing Project

Dementia and Geriatric Cognitive Disorders
Elizabeth E Blueon behalf of the Alzheimer’s Disease Sequencing Project

Abstract

The Alzheimer's Disease Sequencing Project (ADSP) aims to identify novel genes influencing Alzheimer's disease (AD). Variants within genes known to cause dementias other than AD have previously been associated with AD risk. We describe evidence of co-segregation and associations between variants in dementia genes and clinically diagnosed AD within the ADSP. We summarize the properties of known pathogenic variants within dementia genes, describe the co-segregation of variants annotated as "pathogenic" in ClinVar and new candidates observed in ADSP families, and test for associations between rare variants in dementia genes in the ADSP case-control study. The participants were clinically evaluated for AD, and they represent European, Caribbean Hispanic, and isolate Dutch populations. Pathogenic variants in dementia genes were predominantly rare and conserved coding changes. Pathogenic variants within ARSA, CSF1R, and GRN were observed, and candidate variants in GRN and CHMP2B were nominated in ADSP families. An independent case-control study provided evidence of an association between variants in TREM2, APOE, ARSA, CSF1R, PSEN1, and MAPT and risk of AD. Variants in genes which cause dementing disorders may influence the clinical d...Continue Reading

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Citations

Dec 7, 2018·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Xiaoling ZhangLindsay A Farrer
May 2, 2020·Journal of Neuropathology and Experimental Neurology·Peter T NelsonYuriko Katsumata
Feb 2, 2020·Interdisciplinary Sciences, Computational Life Sciences·Fuzhang YangJiang Xie
Apr 3, 2019·Annual Review of Public Health·Kimberly C PaulBeate R Ritz
Nov 22, 2019·Journal of Neuropathology and Experimental Neurology·Yuriko KatsumataPeter T Nelson
Jan 5, 2021·Journal of Genetic Counseling·Bradley RolfSuman Jayadev
Dec 7, 2021·Frontiers in Aging Neuroscience·Banglian HuHonghua Zheng
Jan 4, 2022·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Dolly Reyes-DumeyerRichard Mayeux

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