The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity
Niccolò Tesi (Vrije Universiteit Amsterdam, TU Delft - Pattern Recognition and Bioinformatics)
Marc Hulsman (Vrije Universiteit Amsterdam, TU Delft - Pattern Recognition and Bioinformatics)
Sven J. van der Lee (Vrije Universiteit Amsterdam)
Iris E. Jansen (Vrije Universiteit Amsterdam)
Najada Stringa (Vrije Universiteit Amsterdam)
Natasja M. van Schoor (Vrije Universiteit Amsterdam)
Philip Scheltens (Vrije Universiteit Amsterdam)
Marcel J.T. Reinders (TU Delft - Pattern Recognition and Bioinformatics)
Henne Holstege (TU Delft - Intelligent Systems, Vrije Universiteit Amsterdam, Amsterdam UMC)
undefined More Authors (External organisation)
More Info
expand_more
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
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.
help_outline