1. The Effect of Alzheimer's Disease-Associated Genetic Variants on Longevity.
- Author
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Tesi, Niccolò, Hulsman, Marc, van der Lee, Sven J., Jansen, Iris E., Stringa, Najada, van Schoor, Natasja M., Scheltens, Philip, van der Flier, Wiesje M., Huisman, Martijn, Reinders, Marcel J. T., and Holstege, Henne
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LONGEVITY ,GENETIC variation ,OLD age ,ALZHEIMER'S disease ,CENTENARIANS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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