ArticleJAMA neurology2014
Common genetic variants on 6q24 associated with exceptional episodic memory performance in the elderly.
Article in JAMA neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- What characterizes the exceptional cognition of superagers? A systematic review of multidomain biomarkers of successful cognitive aging.The Gerontologist · 2026Pooled it
- Association between late maternal age and age-related endophenotypes in the Long Life Family Study.Neuroscience letters · 2022Article
- NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Alzheimer's Disease Variant Portal: A Catalog of Genetic Findings for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Article
- Patterns of multi-domain cognitive aging in participants of the Long Life Family Study.GeroScience · 2020Article
- Article
- Age-Related Biomarkers in LLFS Families With Exceptional Cognitive Abilities.The journals of gerontology. Series A, Biological sciences and medical sciences · 2017Article
- Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging.Frontiers in immunology · 2016Review
- A call for new thoughts about what might influence human brain aging: aging, apolipoprotein E, and amyloid.JAMA neurology · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
importanceThere are genetic influences on memory ability as we age, but no specific genes have been identified.
objectiveTo use a cognitive endophenotype, exceptional episodic memory (EEM) performance, derived from nondemented offspring from the Long Life Family Study (LLFS) to identify genetic variants that may be responsible for the high cognitive performance of LLFS participants and further replicate these variants using an additional 4006 nondemented individuals from 4 independent elderly cohorts. DESIGN, SETTING, AND
participantsA total of 467 LLFS participants from 18 families with 2 or more offspring that exhibited exceptional memory performance were used for genome-wide linkage analysis. Adjusted multivariate linear analyses in the 40-megabase region encompassing the linkage peak were conducted using 4 independent replication data sets that included 4006 nondemented elderly individuals. Results of the individual replication cohorts were combined by meta-analysis.
main outcome measureEpisodic memory scores computed as the mean of the 2 standardized measures of Logical Memory IA and IIA.
resultsHeritability estimates indicated a significant genetic component for EEM (h2 = 0.21; SE = 0.09). Genome-wide linkage analysis revealed that EEM was linked to the 6q24 region (maximum logarithm of odds score, 3.64). Association analysis in LLFS families identified single-nucleotide polymorphisms (SNPs) nominally associated with EEM in the 40-megabase window encompassing the linkage peak. Replication in one cohort identified a set of 26 SNPs associated with episodic memory (P ≤ .05). Meta-analysis of the 26 SNPs using the 4 independent replication cohorts found SNPs rs9321334 and rs6902875 to be nominally significantly associated with episodic memory (P = .009 and P = .013, respectively). With meta-analysis restricted to individuals lacking an APOE ε4 allele, SNP rs6902875 became statistically significant (meta-analysis, P = 6.7 × 10-5). Haplotype analysis incorporating the 2 SNPs flanking rs6902875 (rs9321334 and rs4897574) revealed that the A-A-C haplotype was significantly associated with episodic memory performance (P = 2.4 × 10-5). This genomic region harbors monooxygenase dopamine β-hydroxylase-like 1 gene (MOXD1), implicated in the biosynthesis of norepinephrine, which is prominently involved in cognitive functions. CONCLUSIONS AND RELEVANCE: The results provide strong evidence for potential candidate genes related to EEM on 6q24. Identifying the genes will help in understanding the biological basis of memory performance and allow interventions for enhancement of cognitive function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.