The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity

Tesi, Niccolò and Hulsman, Marc and van der Lee, Sven J. and Jansen, Iris E. and Stringa, Najada and van Schoor, Natasja M. and Scheltens, Philip and van der Flier, Wiesje M. and Huisman, Martijn and Reinders, Marcel J. T. and Holstege, Henne (2021) The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity. Frontiers in Genetics, 12. ISSN 1664-8021

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Abstract

Human longevity is influenced by the genetic risk of age-related diseases. As Alzheimer’s disease (AD) represents a common condition at old age, an interplay between genetic factors affecting AD and longevity is expected. We explored this interplay by studying the prevalence of AD-associated single-nucleotide-polymorphisms (SNPs) in cognitively healthy centenarians, and replicated findings in a parental-longevity GWAS. We found that 28/38 SNPs that increased AD-risk also associated with lower odds of longevity. For each SNP, we express the imbalance between AD- and longevity-risk as an effect-size distribution. Based on these distributions, we grouped the SNPs in three groups: 17 SNPs increased AD-risk more than they decreased longevity-risk, and were enriched for β-amyloid metabolism and immune signaling; 11 variants reported a larger longevity-effect compared to their AD-effect, were enriched for endocytosis/immune-signaling, and were previously associated with other age-related diseases. Unexpectedly, 10 variants associated with an increased risk of AD and higher odds of longevity. Altogether, we show that different AD-associated SNPs have different effects on longevity, including SNPs that may confer general neuro-protective functions against AD and other age-related diseases.

Item Type: Article
Subjects: Pacific Library > Medical Science
Depositing User: Unnamed user with email support@pacificlibrary.org
Date Deposited: 12 Jan 2023 08:43
Last Modified: 05 Jun 2024 10:37
URI: http://editor.classicopenlibrary.com/id/eprint/35

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