Failure to replicate effect of kibra on human memory in two large cohorts of European origin

Need, Anna C.; Attix, Deborah K.; McEvoy, Jill M.; Cirulli, Elizabeth T.; Linney, Kristen N.; Wagoner, Ana Patricia; Gumbs, Curtis; Giegling, Ina; Möller, Hans‐Jürgen; Francks, Clyde; Muglia, Pierandrea; Roses, Allen D.; Gibson, Greg; Weale, Michael E.; Rujescu, Dan; Goldstein, David B.

doi:10.1002/ajmg.b.30658

Cited by 64 publications

(54 citation statements)

References 7 publications

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“…This result confirms the original finding by Papassotiropoulos et al (2006) and data from several subsequent studies (Almeida et al, 2008;Bates et al, 2009;Corneveaux et al, in press;Schaper et al, 2008), although another recent investigation failed to find significant effects of the KIBRA polymorphism on episodic memory performance in two independent samples (Need et al, 2008).…”

Section: Discussionsupporting

confidence: 89%

“…However, another study failed to confirm an association between the KIBRA polymorphism and episodic memory in two independent samples (Need et al, 2008), and a study in adolescents also genotyped the KIBRA polymorphism but did not report any significant association between KIBRA status and episodic memory (Jacobsen, Picciotto, Heath, Mencl, & Gelernter, 2009). Further, an opposite effect of higher episodic memory performance in non-T carriers was found in a sample of elderly participants with subjective memory complaints (Nacmias et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

Preuschhof

Heekeren

et al. 2010

Neuropsychologia

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a b s t r a c tIndividual differences in episodic memory are highly heritable. Several studies have linked a polymorphism in the gene encoding the KIBRA protein to episodic memory performance. Results regarding CLSTN2, the gene encoding the synaptic protein calsyntenin 2, have been less consistent, possibly pointing to interactions with other genes. Given that both KIBRA and CLSTN2 are expressed in the medial temporal lobe and have been linked to synaptic plasticity, we investigated whether KIBRA and CLSTN2 interactively modulate episodic memory performance (n = 383). We replicated the beneficial effect of the KIBRA T-allele on episodic memory, and discovered that this effect increases with the associative demands of the memory task. Importantly, the memory-enhancing effect of the KIBRA T-allele was boosted by the presence of the CLSTN2 C-allele, which positively affected memory performance in some previous studies. In contrast, the presence of CLSTN2 C-allele led to reduced performance in subjects homozygous for the KIBRA C-allele. Overall, these findings suggest that KIBRA and CLSTN2 interactively modulate episodic memory performance, and underscore the need for delineating the interactive effects of multiple genes on brain and behavior.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

Preuschhof

Heekeren

et al. 2010

Neuropsychologia

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“…One genome-wide association study did report significant associations between delayed recall and variants in the KIBRA and CAMTA1 6,7 genes, but these associations have not been replicated. 8 Two other genome-wide association studies on cognition did not show conclusive associations. 9,10 Although it seems clear that genetic variation strongly influences cognitive performance in human beings, identification of important genetic differences remains elusive.…”

Section: Introductionmentioning

confidence: 96%

Common genetic variation and performance on standardized cognitive tests

et al. 2010

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One surprising feature of the recently completed waves of genome-wide association studies is the limited impact of common genetic variation in individually detectable polymorphisms on many human traits. This has been particularly pronounced for studies on psychiatric conditions, which have failed to produce clear, replicable associations for common variants. One popular explanation for these negative findings is that many of these traits may be genetically heterogeneous, leading to the idea that relevant endophenotypes may be more genetically tractable. Aspects of cognition may be the most important endophenotypes for psychiatric conditions such as schizophrenia, leading many researchers to pursue large-scale studies on the genetic contributors of cognitive performance in the normal population as a surrogate for aspects of liability to disease. Here, we perform a genomewide association study with two tests of executive function, Digit Symbol and Stroop Color-Word, in 1086 healthy volunteers and with an expanded cognitive battery in 514 of these volunteers. We show that, consistent with published studies of the psychiatric conditions themselves, no single common variant has a large effect (explaining 44-8% of the population variation) on the performance of healthy individuals on standardized cognitive tests. Given that these are important endophenotypes, our work is consistent with the idea that identifying rare genetic causes of psychiatric conditions may be more important for future research than identifying genetically homogenous endophenotypes.

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“…The T allele of a common KIBRA (WW and C2 domain containing 1) C/T polymorphism (rs17070145) was first linked to increased episodic memory performance in a genomewide association study and two independent replication samples by Papassotiropoulos and colleagues (2006). In subsequent studies, the T allele has been associated with increased episodic memory performance (Bates et al, 2009;Preuschhof et al, 2010;Vassos et al, 2010; but see Need et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

KIBRA Polymorphism Is Related to Enhanced Memory and Elevated Hippocampal Processing

Kauppi

Nilsson²,

Adolfsson³

et al. 2011

J. Neurosci.

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Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N ϭ 2230) and fMRI (N ϭ 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N ϭ 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.

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Failure to replicate effect of kibra on human memory in two large cohorts of European origin

Cited by 64 publications

References 7 publications

KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

Common genetic variation and performance on standardized cognitive tests

KIBRA Polymorphism Is Related to Enhanced Memory and Elevated Hippocampal Processing

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