Association of <i>KIBRA</i> with episodic and working memory: A meta‐analysis

Milnik, Annette; Heck, Angela; Vogler, Christian; Heinze, Hans‐Jochen; Quervain, Dominique J.‐F. de; Papassotiropoulos, Andreas

doi:10.1002/ajmg.b.32101

Cited by 84 publications

(96 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As our studies continue to collect data, it will facilitate a more detailed examination of the influence of genetic variation in KIBRA and CLSTN2 on longitudinal memory performance and change in hippocampal volume. Also, even when we combined our cohorts to increase statistical power our sample size was relatively small, and a recent study indicated that in order to have 80 % power to detect an effect of KIBRA on episodic memory it requires a sample size of ~2000 individuals (Milnik et al, 2012). However, our subsample with hippocampal volume data was comparatively larger than most other studies previously reported (e.g.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

et al. 2015

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure.However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145, rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippocampal volume, nor did variation in these genes influence longitudinal memory decline or hippocampal atrophy in two cohorts of older adults.

show abstract

Section: Discussionmentioning

confidence: 97%

“…Thus, the effect of the KIBRA SNP, rs17070145, on memory performance is still unclear, as indicated by a recent meta-analysis (Milnik et al, 2012) and review (Schwab et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Consequently, behavioral genetics studies have identified and characterized genetic variations associated with human memory performance [2,3]. These findings have been generated either by candidate-gene studies [4][5][6][7], which depend on pre-existing information, or by genome-wide association studies (GWAS), which allow to identify novel memory-related genes and molecular pathways [8,9]. However, memory performance is not a result of a single cognitive process, but rather the outcome of many, such as memory encoding, forgetting, or modulation of memory strength by emotional arousal.…”

Section: Introductionmentioning

confidence: 99%

Correction: BAIAP2 Is Related to Emotional Modulation of Human Memory Strength

2014

PLoS ONE

View full text Add to dashboard Cite

Memory performance is the result of many distinct mental processes, such as memory encoding, forgetting, and modulation of memory strength by emotional arousal. These processes, which are subserved by partly distinct molecular profiles, are not always amenable to direct observation. Therefore, computational models can be used to make inferences about specific mental processes and to study their genetic underpinnings. Here we combined a computational model-based analysis of memory-related processes with high density genetic information derived from a genome-wide study in healthy young adults. After identifying the best-fitting model for a verbal memory task and estimating the best-fitting individual cognitive parameters, we found a common variant in the gene encoding the brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) that was related to the model parameter reflecting modulation of verbal memory strength by negative valence. We also observed an association between the same genetic variant and a similar emotional modulation phenotype in a different population performing a picture memory task. Furthermore, using functional neuroimaging we found robust genotype-dependent differences in activity of the parahippocampal cortex that were specifically related to successful memory encoding of negative versus neutral information. Finally, we analyzed cortical gene expression data of 193 deceased subjects and detected significant BAIAP2 genotype-dependent differences in BAIAP2 mRNA levels. Our findings suggest that model-based dissociation of specific cognitive parameters can improve the understanding of genetic underpinnings of human learning and memory.

show abstract

“…Although many genetic variations associated with human memory performance have been identified (3)(4)(5)(6)(7)(8)(9), most were based on general memory scores, such as the number of recalled items. Such scores may serve as good correlates of overall memory ability, but they offer little insight into the genetic underpinnings of specific memory-related mental processes, such as encoding, memory maintenance, modulation by emotional arousal, or guessing strategies.…”

mentioning

confidence: 99%

“…GWAS already had identified a number of associations between single genetic markers and cognitive traits, such as episodic memory (7)(8)(9) and modulation of memory strength by negative emotional arousal (21). However, because many such traits are complex and multigenic, it is unlikely that a single genetic variant will explain a sufficient amount of behavioral variability.…”

mentioning

confidence: 99%

Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Luksys

Fastenrath

Coynel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.learning and memory | computational model | gene set enrichment analysis | functional neuroimaging | frontal lobe H uman memory is a highly heritable and complex trait that is the outcome of numerous neurocognitive processes (1, 2). Although many genetic variations associated with human memory performance have been identified (3-9), most were based on general memory scores, such as the number of recalled items. Such scores may serve as good correlates of overall memory ability, but they offer little insight into the genetic underpinnings of specific memory-related mental processes, such as encoding, memory maintenance, modulation by emotional arousal, or guessing strategies. Importantly, neurobiological and molecular profiles of such processes are known to be partly distinct (10-12). Because some of the mental processes involved in memory are not readily amenable to direct observation, computational modeling can be used to make inferences about them (13,14). Modelbased analyses provided insights into neurocomputational mechanisms of reward-based learning and decision making (15-17), related model parameters such as the learning rate to genetic polymorphisms (18,19), and provided a computational explanation for the inverted-U-shaped relation between stress intensity and behavioral performance (20). As a relatively recent development, the model-based analysis approach has largely been missing from studies of human episodic memory and genome-wide association studies (GWAS).GWAS already had identified a number of associations betwee...

show abstract

Association of KIBRA with episodic and working memory: A meta‐analysis

Cited by 84 publications

References 61 publications

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

Correction: BAIAP2 Is Related to Emotional Modulation of Human Memory Strength

Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Contact Info

Product

Resources

About