AI Article Synopsis
- - The study explores how rare genetic variations contribute to Alzheimer's disease (AD) related traits, even though this area has not received much focus before.
- - Researchers conducted rare-variant association studies on genetic data from two different studies involving a total of 1,258 participants to identify any significant associations with Alzheimer's traits.
- - They discovered a new mutation possibly linked to AD and found significant genetic contributions from specific genes (RBKS and OR7A10) to cognitive performance and brain changes, which could help in developing new treatments and diagnostic methods for AD.
Article Abstract
Introduction: Despite increasing evidence of a role of rare genetic variation in the risk of Alzheimer's disease (AD), limited attention has been paid to its contribution to AD-related biomarker traits indicative of AD-relevant pathophysiological processes.
Methods: We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808).
Results: Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively.
Discussion: The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets.
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| http://dx.doi.org/10.1002/alz.12842 | DOI Listing |
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