KIBRA and APOE Gene Variants Affect Brain Functional Network Connectivity in Healthy Older People

: Genetic factors play a critical role in the development of Alzheimer's disease (AD). Kidney and brain expressed protein (KIBRA) and apolipoprotein E (APOE) are involved in episodic memory performance and AD. However, the interactions between KIBRA and APOE on brain functional network connectivity (FNC) remain unknown in healthy older people. Using independent component analysis, we systematically investigated additive and epistatic interactions of KIBRA rs1707045 and APOE on FNC in 170 healthy older Chinese people of Han ethnicity. We found significant additive KIBRA-APOE interactions on brain FNC in the right medial prefrontal cortex, the posterior cingulate cortex in the default-mode network, and the dorsal anterior cingulate cortex in the salience network. We also found significant epistatic KIBRA-APOE interactions on brain FNC in the left superior frontal gyrus and left angular gyrus in default-mode network. No significant KIBRA-APOE interactions were detected in other brain resting-state networks. These findings suggest that healthy older people have additive and epistatic interactions of KIBRA and APOE gene variants, which modulate brain FNC and may partly elucidate their association with episodic memory performance and AD.