Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis.
Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis.
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DOI：
10.1038/s41467-023-36605-x
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发表时间：
2023-02-20
影响因子：
16.6
通讯作者：
Smoller, Jordan W.
中科院分区：
文献类型：
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作者：
Grotzinger, Andrew D.;Mallard, Travis T.;Liu, Zhaowen;Seidlitz, Jakob;Ge, Tian;Smoller, Jordan W.
最近的成像遗传学研究表明，皮质厚度 (CT) 和表面积 (SA) 的皮质区域内存在高度遗传重叠。我们通过应用基因组结构方程模型（基因组 SEM）对这种遗传关系的多变量系统进行建模，并简单地定义了 CT 和 SA 背后的五个基因组大脑因素以及捕获所有大脑区域遗传重叠的通用因素。我们通过证明模型对半独立样本的普遍性来验证这些因素，并表明这些因素与大脑皮层的生物学和功能相关分区一致。我们应用分层基因组 SEM 来识别特定类别的基因（例如神经元细胞类型），这些基因与大脑区域特定亚群的多效性不成比例地相关，如基因组因素所索引。最后，我们检查了与精神和认知相关的遗传关联，发现认知功能的广泛方面与 SA 的一般因素相关，而精神关联为零。这些分析为大脑皮层两个关键特征的多变量基因组结构提供了重要见解。目前的研究确定了大脑皮层厚度和表面积的五个基因组亚群，其特征是高水平的共享遗传信号。这些子簇映射到皮质的生物和功能分区。
Recent work in imaging genetics suggests high levels of genetic overlap within cortical regions for cortical thickness (CT) and surface area (SA). We model this multivariate system of genetic relationships by applying Genomic Structural Equation Modeling (Genomic SEM) and parsimoniously define five genomic brain factors underlying both CT and SA along with a general factor capturing genetic overlap across all brain regions. We validate these factors by demonstrating the generalizability of the model to a semi-independent sample and show that the factors align with biologically and functionally relevant parcellations of the cortex. We apply Stratified Genomic SEM to identify specific categories of genes (e.g., neuronal cell types) that are disproportionately associated with pleiotropy across specific subclusters of brain regions, as indexed by the genomic factors. Finally, we examine genetic associations with psychiatric and cognitive correlates, finding that broad aspects of cognitive function are associated with a general factor for SA and that psychiatric associations are null. These analyses provide key insights into the multivariate genomic architecture of two critical features of the cerebral cortex. The current study identifies five genomic subclusters of brain regions for cortical thickness and surface area characterized by high levels of shared genetic signal. These subclusters map onto biological and functional parcellations of the cortex.
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影响因子：
5.7
作者：
Karama, Sherif;Colom, Roberto;Johnson, Wendy;Deary, Ian J.;Haier, Richard;Waber, Deborah P.;Lepage, Claude;Ganjavi, Hooman;Jung, Rex;Evans, Alan C.
通讯作者：
Evans, Alan C.
影响因子：
11
作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
通讯作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
64.8
作者：
通讯作者：
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