Larger cerebral cortex is genetically correlated with greater frontal area and dorsal thickness.
Larger cerebral cortex is genetically correlated with greater frontal area and dorsal thickness.
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较大的大脑皮层在遗传上与较大的额叶区域和背侧厚度相关。
DOI：
10.1073/pnas.2214834120
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发表时间：
2023-03-14
影响因子：
11.1
通讯作者：
Chen, Chi-Hua
中科院分区：
文献类型：
--
作者：
Makowski, Carolina;Wang, Hao;Srinivasan, Anjali;Qi, Anna;Qiu, Yuqi;van der Meer, Dennis;Frei, Oleksandr;Zou, Jingjing;Visscher, Peter M.;Yang, Jian;Chen, Chi-Hua
在分析大脑MRI数据时，调整与保留全局测量一直是一个长期存在的问题，并且可能对大脑皮层的基因组研究产生重要影响。针对全局测量进行调整可确保感兴趣区域的结果不会受到整体较大大脑尺寸的混淆。然而，当总量和区域指标相关时，调整全球指标可能会丢失重要信号。我们表明，保留与调整全球大脑的基因组研究的措施影响基因的发现，特别是额顶叶皮层。了解有助于人类大脑中扩展关联区域的遗传因素，例如前额叶皮层，可以帮助提供对人类高级认知及其与其他物种相比的独特发展的机械见解。人类大脑皮层的扩张在整个大脑中是不均匀的。我们通过比较24个皮质区域的两组全基因组关联研究，评估了皮质全局扩展和区域化的遗传结构，其中对全局测量进行了调整和未进行调整（即，总表面积，平均皮质厚度）。我们发现393和756个显着的基因座，调整和不调整全局，分别为8%和45%的基因座与一个以上的地区。未调整全局的分析结果恢复了与全局测量相关的位点。遗传因素，有助于总表面积的皮质特别扩大前/额区，而那些有助于较厚的皮质主要增加背/额顶叶厚度。基于相互作用组的分析显示，全球和背外侧前额叶模块，丰富的神经发育和免疫系统的途径显着的遗传重叠。考虑全球措施是重要的，在了解遗传变异的皮质形态。
Adjusting vs. retaining global measures in analysis of brain MRI data has been a long-standing question and can have important implications for genomic studies of the cortex. Adjusting for global measures ensures that results for regions of interest are not confounded by overall larger brain size. However, adjusting for globals may throw away important signal when total and regional measures are correlated. We show that retaining vs. adjusting for global brain measures in genomic studies impacts gene discovery, particularly for fronto-parietal cortex. Understanding the genetic factors that contribute to expanded association areas in the human brain, such as the prefrontal cortex, can help provide mechanistic insight into higher human cognition and its unique development compared to other species. Human cortical expansion has occurred non-uniformly across the brain. We assessed the genetic architecture of cortical global expansion and regionalization by comparing two sets of genome-wide association studies of 24 cortical regions with and without adjustment for global measures (i.e., total surface area, mean cortical thickness) using a genetically informed parcellation in 32,488 adults. We found 393 and 756 significant loci with and without adjusting for globals, respectively, where 8% and 45% loci were associated with more than one region. Results from analyses without adjustment for globals recovered loci associated with global measures. Genetic factors that contribute to total surface area of the cortex particularly expand anterior/frontal regions, whereas those contributing to thicker cortex predominantly increase dorsal/frontal-parietal thickness. Interactome-based analyses revealed significant genetic overlap of global and dorsolateral prefrontal modules, enriched for neurodevelopmental and immune system pathways. Consideration of global measures is important in understanding the genetic variants underlying cortical morphology.
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DOI：
10.1073/pnas.0402680101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Gogtay, N;Giedd, JN;Thompson, PM
通讯作者：
Thompson, PM
影响因子：
64.5
作者：
Brose, K;Bland, KS;Kidd, T
通讯作者：
Kidd, T
影响因子：
64.8
作者：
Elliott LT;Sharp K;Alfaro-Almagro F;Shi S;Miller KL;Douaud G;Marchini J;Smith SM
通讯作者：
Smith SM
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：
16.2
作者：
Cadwell, Cathryn R.;Bhaduri, Aparna;Mostajo-Radji, Mohammed A.;Keefe, Matthew G.;Nowakowski, Tomasz J.
通讯作者：
Nowakowski, Tomasz J.