A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population.
A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population.
复制标题
在大量中国人群中发现了与精神分裂症相关的遗传脑认知通路
DOI：
10.1016/j.ebiom.2018.10.009
复制
发表时间：
2018-11
期刊：
影响因子：
11.1
通讯作者：
Jiang T
中科院分区：
文献类型：
--
作者：
Luo N;Sui J;Chen J;Zhang F;Tian L;Lin D;Song M;Calhoun VD;Cui Y;Vergara VM;Zheng F;Liu J;Yang Z;Zuo N;Fan L;Xu K;Liu S;Li J;Xu Y;Liu S;Lv L;Chen J;Chen Y;Guo H;Li P;Lu L;Wan P;Wang H;Wang H;Yan H;Yan J;Yang Y;Zhang H;Zhang D;Jiang T
在过去几十年中，人们付出了巨大努力来探索精神分裂症中大脑结构/功能异常以及认知障碍的遗传影响。在这项工作中，我们旨在扩展先前的研究，以在中国的一个大型数据集中探索遗传因素、大脑特征和认知评分之间的内在中介途径。
对905名中国受试者的灰质（GM）体积、低频波动振幅分数（fALFF）以及4522个精神分裂症易感单核苷酸多态性（SNP）进行了联合分析，以研究多模态关联。基于所确定的影像 - 遗传模式，随后进行了与认知的相关性分析和中介分析，以揭示潜在的中介途径。
一种相关的影像 - 遗传模式被确定具有组间判别性，它还与工作记忆表现相关。特别是，精神分裂症患者丘脑、壳核和双侧颞回的灰质减少与内侧前额叶皮质的fALFF降低相关，两者还都与富集在神经元发育、突触组织和轴突通路的遗传因素相关，突出的基因包括CSMD1、CNTNAP2、DCC、GABBR2等。这种相关模式在一个独立队列（166名受试者）中也得到了重复，尽管该队列与发现队列存在一定的年龄和临床差异。进一步的中介分析表明，灰质改变显著中介了从SNP到fALFF的关联，而fALFF中介了从SNP和灰质到工作记忆表现的关联。
这项研究不仅验证了精神分裂症中受损的影像 - 遗传关联，还初步揭示了一种潜在的遗传 - 大脑 - 认知中介途径，表明多基因风险因素可以对从大脑结构到功能的表型指标产生影响，从而进一步影响精神分裂症患者的认知。
In the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among genetic factor, brain features and cognitive scores in a large Chinese dataset. Gray matter (GM) volume, fractional amplitude of low-frequency fluctuations (fALFF), and 4522 schizophrenia-susceptible single nucleotide polymorphisms (SNP) from 905 Chinese subjects were jointly analyzed, to investigate the multimodal association. Based on the identified imaging-genetic pattern, correlations with cognition and mediation analysis were then conducted to reveal the potential mediation pathways. One linked imaging-genetic pattern was identified to be group discriminative, which was also associated with working memory performance. Particularly, GM reduction in thalamus, putamen and bilateral temporal gyrus in schizophrenia was associated with fALFF decrease in medial prefrontal cortex, both were also associated with genetic factors enriched in neuron development, synapse organization and axon pathways, highlighting genes including CSMD1, CNTNAP2, DCC, GABBR2 etc. This linked pattern was also replicated in an independent cohort (166 subjects), which although showed certain age and clinical differences with the discovery cohort. A further mediation analysis suggested that GM alterations significantly mediated the association from SNP to fALFF, while fALFF mediated the association from SNP and GM to working memory performance. This study has not only verified the impaired imaging-genetic association in schizophrenia, but also initially revealed a potential genetic-brain-cognition mediation pathway, indicating that polygenic risk factors could exert impact on phenotypic measures from brain structure to function, thus could further affect cognition in schizophrenia.
登录
查看更多内容
影响因子：
4.7
作者：
Calhoun VD;Sui J;Kiehl K;Turner J;Allen E;Pearlson G
通讯作者：
Pearlson G
影响因子：
--
作者：
Gur, RE;Cowell, PE;Gur, RC
通讯作者：
Gur, RC
影响因子：
3.7
作者：
Green, Adam E.;Kraemer, David J. M.;Gray, Jeremy R.
通讯作者：
Gray, Jeremy R.
影响因子：
--
作者：
Cannon, TD;Hennah, W;Peltonen, L
通讯作者：
Peltonen, L
影响因子：
64.8
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
通讯作者：
Collins, Francis S.