APOE and KIBRA Interactions on Brain Functional Connectivity in Healthy Young Adults
APOE and KIBRA Interactions on Brain Functional Connectivity in Healthy Young Adults
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APOE 和 KIBRA 相互作用对健康年轻人大脑功能连接的影响
DOI：
10.1093/cercor/bhw276
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发表时间：
2016-09
期刊：
影响因子：
3.7
通讯作者：
Chunshui Yu
中科院分区：
文献类型：
--
作者：
Wen Qin;Bing Liu;Tianzi Jiang;Chunshui Yu
APOE和KIBRA的遗传变异与人类记忆和阿尔茨海默病有关。APOE和KIBRA可以联合调节谷氨酸受体影响长时程增强，但它们在脑功能连接中的相互作用尚不清楚。在这里，我们研究了267名健康年轻人的APOE和KIBRA（rs 17070145）对脑功能连接密度（FCD）的加性和上位性相互作用。进行基于体素的FCD分析以识别具有显著APOE-KIBRA相互作用的脑区域。累加效应显示，随着APOE和KIBRA危险等位基因数目的增加，左侧海马旁回和右侧颞中回FCD降低，双侧枕中回FCD增加。在背外侧前额叶皮层（DLPFC）的FCD中，APOE与KIBRA之间存在上位性相互作用。DLPFC的FCD显示KIBRA TT纯合子中APOE风险等位基因依赖性降低（ε2 > ε3 > ε4），而KIBRA C携带者中APOE风险等位基因依赖性增加（ε2 < ε3 < ε4）。在加性和上位性分析中，FCD差异仅在2个极端亚组之间具有显著性。这些发现表明，APOE和KIBRA对健康年轻人的大脑连接具有区域依赖性的加性和上位性相互作用。
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.
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影响因子：
2.9
作者：
Thomas, G;Sinville, R;Barany, F
通讯作者：
Barany, F
影响因子：
7.6
作者：
A. V. Witte;T. Köbe;Lucia Kerti;D. Rujescu;A. Flöel
通讯作者：
A. V. Witte;T. Köbe;Lucia Kerti;D. Rujescu;A. Flöel
影响因子：
2.9
作者：
Hafkemeijer A;Möller C;Dopper EG;Jiskoot LC;Schouten TM;van Swieten JC;van der Flier WM;Vrenken H;Pijnenburg YA;Barkhof F;Scheltens P;van der Grond J;Rombouts SA
通讯作者：
Rombouts SA
影响因子：
4.2
作者：
Alexander GE;Bergfield KL;Chen K;Reiman EM;Hanson KD;Lin L;Bandy D;Caselli RJ;Moeller JR
通讯作者：
Moeller JR
影响因子：
9.9
作者：
Honea, R. A.;Swerdlow, R. H.;Burns, J. M.
通讯作者：
Burns, J. M.