A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene

• Published in: Molecular psychiatry Vol. 18; no. 2; pp. 255 - 263
• Main Authors: Papassotiropoulos, A, Stefanova, E, Vogler, C, Gschwind, L, Ackermann, S, Spalek, K, Rasch, B, Heck, A, Aerni, A, Hanser, E, Demougin, P, Huynh, K-D, Luechinger, R, Klarhöfer, M, Novakovic, I, Kostic, V, Boesiger, P, Scheffler, K, de Quervain, D J-F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2013; Nature Publishing Group
• Subjects: 631/378/1595; 631/378/2583; 692/700/1421/65; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Behavioral Sciences; Biological Psychology; Brain - blood supply; Brain - physiology; Cognition & reasoning; Cohort Studies; Female; Gene expression; Gene Expression - genetics; Genetic aspects; Genetic testing; Genetic variation; Genome-Wide Association Study; Genomes; Genotype; Genotype & phenotype; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Memory; Memory - physiology; Neuroimaging; Neurosciences; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Original; original-article; Oxygen - blood; Pharmacotherapy; Polymorphism, Single Nucleotide - genetics; Proteins; Psychiatry; Psychological aspects; RNA, Messenger - metabolism; Serbia; Switzerland; University students; Verbal Learning - physiology; Young adults; Serbia; Switzerland; Germany; Basel Switzerland; fMRI; beta-catenin-like; GWAS; memory
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2011.148

Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 ( CTNNBL1 ) was significantly ( P =7 × 10 −8 ) associated with verbal memory performance in a cognitively healthy cohort from Switzerland ( n =1073) and was replicated in a second cohort from Serbia ( n =524; P =0.003). Gene expression studies showed CTNNBL1 genotype-dependent differences in beta-catenin-like protein 1 mRNA levels in the human cortex. Functional magnetic resonance imaging in 322 subjects detected CTNNBL1 genotype-dependent differences in memory-related brain activations. Converging evidence from independent experiments and different methodological approaches suggests a role for CTNNBL1 in human memory.