Common Kibra Alleles Are Associated with Human Memory Performance
Andreas Papassotiropoulos,1,3*
Dietrich A. Stephan,3*
Matthew J. Huentelman,3
Frederic J. Hoerndli,1
David W. Craig,3
John V. Pearson,3
Kim-Dung Huynh,1
Fabienne Brunner,1
Jason Corneveaux,3
David Osborne,4
M. Axel Wollmer,1
Amanda Aerni,1
Daniel Coluccia,1
Jürgen Hänggi,1
Christian R. A. Mondadori,1
Andreas Buchmann,1
Eric M. Reiman,3,6
Richard J. Caselli,5
Katharina Henke,1
Dominique J.-F. de Quervain1,2
Human memory is a polygenic trait. We performed a genome-wide screen to identify memory-related gene variants. A genomic locus encoding the brain protein KIBRA was significantly associated with memory performance in three independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures. Functional magnetic resonance imaging detected KIBRA allele–dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory.
1 Division of Psychiatry Research, University of Zurich, Zurich 8057, Switzerland.
2 Center for Integrative Human Physiology, University of Zurich, Zurich 8057, Switzerland.
3 Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
4 Department of Psychology, Mayo Clinic, Scottsdale, AZ 85259, USA.
5 Department of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USA.
6 The Banner Alzheimer's Institute and the Department of Psychiatry, University of Arizona, Phoenix, AZ 85006, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: papas{at}bli.unizh.ch (A.P.); dstephan{at}tgen.org (D.A.S.)
