Meta-analysis of age-related cognitive decline reveals a novel locus for the attention domain and implicates a COVID-19-related gene for global cognitive function.
Alzheimers Dement
; 2023 Apr 23.
Article
in English
| MEDLINE | ID: covidwho-2290573
ABSTRACT
INTRODUCTION:
Cognitive abilities have substantial heritability throughout life, as shown by twin- and population-based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains.METHODS:
We conducted a meta-analysis on 3045 individuals aged ≥65, derived from three population-based cohorts, to identify genetic variants associated with the decline of five neurocognitive domains (attention, memory, executive function, language, visuospatial function) and global cognitive decline. We also conducted gene-based and functional bioinformatics analyses.RESULTS:
Apolipoprotein E (APOE)4 was significantly associated with decline of memory (p = 5.58E-09) and global cognitive function (p = 1.84E-08). We identified a novel association with attention decline on chromosome 9, rs6559700 (p = 2.69E-08), near RASEF. Gene-based analysis also identified a novel gene, TMPRSS11D, involved in the activation of SARS-CoV-2, to be associated with the decline in global cognitive function (p = 4.28E-07).DISCUSSION:
Domain-specific genetic studies can aid in the identification of novel genes and pathways associated with decline across neurocognitive domains. HIGHLIGHTS rs6559700 was associated with decline of attention. APOE4 was associated with decline of memory and global cognitive decline. TMPRSS11D, a gene involved in the activation of SARS-CoV-2, was implicated in global cognitive decline. Cognitive domain abilities had both unique and shared molecular pathways across the domains.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Cohort study
/
Observational study
/
Prognostic study
/
Reviews
Topics:
Variants
Language:
English
Year:
2023
Document Type:
Article
Affiliation country:
Alz.13064
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