Common genetic variants on 6q24 associated with exceptional episodic memory performance in the elderly
Sandra Barral1, Stephanie Cosentino1, Kaare Christensen2
1G. H. Sergievsky Center, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University Medical Center, New York, New York.
JAMA Neurology
|October 16, 2014
Summary
Researchers identified genetic links to exceptional episodic memory (EEM) in older adults. A specific gene region (6q24) and associated genetic markers may influence memory performance and cognitive function.
Area of Science:
- Neurogenetics
- Cognitive Science
- Human Genetics
Background:
- Aging is associated with genetic influences on memory, but specific genes remain unidentified.
- Exceptional episodic memory (EEM) represents a valuable cognitive endophenotype for genetic research.
Purpose of the Study:
- To identify genetic variants associated with EEM in nondemented offspring from the Long Life Family Study (LLFS).
- To replicate identified genetic variants in an independent cohort of 4006 nondemented elderly individuals.
Main Methods:
- Genome-wide linkage analysis was performed on 467 participants from 18 LLFS families with EEM.
- Association analyses were conducted in a 40-megabase region on chromosome 6q24, followed by meta-analysis of 4 independent replication cohorts.
- Episodic memory scores were calculated using standardized measures of Logical Memory IA and IIA.
Main Results:
- EEM showed a significant genetic component (h2 = 0.21).
- Linkage analysis identified EEM linked to the 6q24 region (LOD score = 3.64).
- SNPs rs9321334 and rs6902875 were nominally associated with episodic memory; rs6902875 reached statistical significance in APOE ε4 non-carriers (P = 6.7 × 10-5). A haplotype (A-A-C) in the MOXD1 gene region was significantly associated with EEM (P = 2.4 × 10-5).
Conclusions:
- The study provides strong evidence for candidate genes on chromosome 6q24 related to EEM.
- Identifying these genes can elucidate the biological basis of memory and inform cognitive enhancement strategies.
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