Common Kibra Alleles Influence Human Episodic Memory Performance
Corneveaux, J.J.1,2; Huentelman, M.J.2; Papassotiropoulos, A.2; Hoerndli, F.J.2; Craig, D.W.2; Pearson, J.V.2; Huynh, K.D.2; Brunner, F.2; Thorburn, A.Q.1; Bracher, D.2; O’Reilly, S.2; Friedman, H.2; Osborne, D.2; Hänggi, J.2; Mondadori, C.R.A.2; Buchmann, A.2; Reiman, E.M.2; Caselli, R.J.2; Henke, K.2; de Quervain, D.J.F.2; and Stephan, D.A.2
1School of Life Sciences, Arizona State University, Tempe, AZ; 2The Translational Genomics Research Institute, Phoenix, AZ
Human memory is a polygenic trait of which approximately 50% is attributed to heritable genetic variability. We performed a whole genome association study at over 500,000 single nucleotide polymorphisms (SNPs) in 351 individuals of Swiss nationality pooled into quartiles based on their performance on a test for episodic memory. A SNP located within the gene KIBRA was significantly associated with both 5-minute (p=4x10-6) and 24-hour (p=0.0008) recall episodic memory performance in two independent, cognitively normal replication cohorts from Switzerland and the United States. The gene expression level of KIBRA in the human brain was found to be highest in the hippocampus and temporal lobe, regions with a well demonstrated link to memory. Additionally, 15 carriers and 15 non-carriers of the rs17070145 T allele, who were matched for 5-minute recall memory performance, were imaged using functional MRI (fMRI) while performing a face-profession associative memory task. It was demonstrated that carriers of the T allele had significantly greater recall-related increases in activity in the hippocampal and parahippocampal regions of the brain. These findings suggest that non-carriers of the T allele must increase activation in these brain regions to reach the same level of memory retrieval performance as carriers of the T allele. Further elucidation of KIBRA=s role in memory enhancement should reveal therapeutic targets for age-related and disease-associated episodic memory decline.