APOE and KIBRA Interactions on Brain Functional Connectivity in Healthy Young Adults.
Genetic variations of APOE and KIBRA have been associated with human memory and Alzheimer's disease. APOE and KIBRA can jointly modulate glutamate receptor to influence long-term potentiation; however, their interactions on brain functional connectivity remain unknown. Here, we investigated additive and epistatic interactions between APOE and KIBRA (rs17070145) on brain functional connectivity density (FCD) in 267 healthy young adults. A voxel-based FCD analysis was performed to identify brain regions with significant APOE-KIBRA interaction. Additive effects showed decreased FCD in the left parahippocampal gyrus and the right middle temporal gyrus and increased FCD in the bilateral middle occipital gyri, with the increase of the number of the risk-alleles of APOE and KIBRA. Epistatic effects showed APOE × KIBRA interaction in the FCD of the dorsolateral prefrontal cortex (DLPFC). The FCD of the DLPFC showed APOE risk-allele-dependent reduction (ε2 > ε3 > ε4) in KIBRA TT homozygotes, but APOE risk-allele-dependent increase (ε2 < ε3 < ε4) in KIBRA C-carriers. FCD differences were only significant between the 2 extreme subgroups in both additive and epistatic analyses. These findings suggest that APOE and KIBRA have region-dependent additive and epistatic interactions on brain connectivity in healthy young adults.
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
Ningnannan
N
Zhang
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
Huaigui
H
Liu
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
Wen
W
Qin
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Bing
B
Liu
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Tianzi
T
Jiang
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
Chunshui
C
Yu
D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008568:Memory / Q000502:physiology; D009483:Neuropsychological Tests; D010750:Phosphoproteins / Q000235:genetics*; D055815:Young Adult
C000612345:ApoE protein, human; D001057:Apolipoproteins E; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C513637:WWC1 protein, human
APOE; KIBRA; functional connectivity density; functional magnetic resonance imaging; genetic interaction