Document detail
ID
oai:www.zora.uzh.ch:229009
Topic
Clinic for Psychiatry, Psychothera... 610 Medicine & healthAuthor
Küçükali, Fahri Neumann, Alexander Van Dongen, Jasper et al Popp, Julius https://orcid.org/0000-0002-0068-0312Langue
engEditor
Wiley-Blackwell Publishing, Inc.
Category
Subjects = 04 Faculty of Medicine
Year
2023
listing date
10/12/2023
Keywords
traits biomarker novel variation rare whole-exome disease alzheimerAbstract
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.
Küçükali, Fahri,Neumann, Alexander,Van Dongen, Jasper,et al,Popp, Julius, https://orcid.org/0000-0002-0068-0312, 2023, Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits, Wiley-Blackwell Publishing, Inc.
