Are Alzheimer's and coronary artery diseases genetically related to longevity?

Bellou, Eftychia and Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483 2023. Are Alzheimer's and coronary artery diseases genetically related to longevity? Frontiers in Psychiatry 13 10.3389/fpsyt.2022.1102347

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Abstract

Introduction: In the last decade researchers have attempted to investigate the shared genetic architecture of longevity and age-related diseases and assess whether the increased longevity in certain people is due to protective alleles in the risk genes for a particular condition or whether there are specific “longevity” genes increasing the lifespan independently of age-related conditions' risk genes. The aim of this study was to investigate the shared genetic component between longevity and two age-related conditions. Methods: We performed a cross-trait meta-analysis of publicly available genome-wide data for Alzheimer's disease, coronary artery disease and longevity using a subset-based approach provided by the R package ASSET. Results: Despite the lack of strong genetic correlation between longevity and the two diseases, we identified 38 genome-wide significant lead SNPs across 22 independent genomic loci. Of them 6 were found to be potentially shared among the three traits mapping to genes including DAB2IP, DNM2, FCHO1, CLPTM1, and SNRPD2. We also identified 19 novel genome-wide associations for the individual traits in this study. Functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants are involved in clathrin-mediated endocytosis and plasma lipoprotein and neurotransmitter clearance processes. Discussion: In summary, we have been able to advance in the knowledge of the genetic overlap existing among longevity and the two most common age-related disorders.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Publisher:	Frontiers Media
ISSN:	1664-0640
Funders:	MRC
Date of First Compliant Deposit:	10 January 2023
Date of Acceptance:	12 December 2022
Last Modified:	10 Jun 2024 08:42
URI:	https://orca.cardiff.ac.uk/id/eprint/155603

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