title: Additive genetic effect of APOE and BDNF on hippocampus activity.
abstract: Human memory is a highly heritable polygenic trait with complex inheritance patterns. To study the genetics of memory and memory-related diseases, hippocampal functioning has served as an intermediate phenotype. The importance of investigating gene-gene effects on complex phenotypes has been emphasized, but most imaging studies still focus on single polymorphisms. APOE ε4 and BDNF Met, two of the most studied gene variants for variability in memory performance and neuropsychiatric disorders, have both separately been related to poorer episodic memory and altered hippocampal functioning. Here, we investigated the combined effect of APOE and BDNF on hippocampal activation (N=151). No non-additive interaction effects were seen. Instead, the results revealed decreased activation in bilateral hippocampus and parahippocampus as a function of the number of APOE ε4 and BDNF Met alleles present (neither, one, or both). The combined effect was stronger than either of the individual effects, and both gene variables explained significant proportions of variance in BOLD signal change. Thus, there was an additive gene-gene effect of APOE and BDNF on medial temporal lobe (MTL) activation, showing that a larger proportion of variance in brain activation attributed to genetics can be explained by considering more than one gene variant. This effect might be relevant for the understanding of normal variability in memory function as well as memory-related disorders associated with APOE and BDNF.
authors: Department of Integrative Medical Biology (Physiology), Umeå University, SE-90187, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden. Electronic address: karolina.kauppi@medisin.uio.
authors: Karolina
authors: K
authors: Kauppi
authors: Department of Psychology, Stockholm University, 106 91 Stockholm, Sweden; Stockholm Brain Institute, Sweden.
authors: Lars-Göran
authors: LG
authors: Nilsson
authors: Aging Research Center (ARC), Karolinska Institutet, Gävlegatan 16, SE-11330 Stockholm, Sweden; Stockholm University, Sweden.
authors: Jonas
authors: J
authors: Persson
authors: Department of Integrative Medical Biology (Physiology), Umeå University, SE-90187, Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden; Department of Radiation Sciences (Diagnostic Radiology), Umeå University, SE-90187 Umeå, Sweden.
authors: Lars
authors: L
authors: Nyberg
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged
chemical_list: D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: APOE; BDNF; Gene–gene effect; Hippocampus; Imaging genetics; fMRI