Using neuroimaging genomics to investigate the evolution of human brain structure.
Using neuroimaging genomics to investigate the evolution of human brain structure.
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DOI：
10.1073/pnas.2200638119
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发表时间：
2022-10-04
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
我们的基因构成的哪些方面促成了人类大脑解剖学的明显特征？在这里，我们基于数万人的神经成像，确定了常见 DNA 变异与皮层回路个体间差异之间的关联，并评估它们与进化兴趣的基因组区域的关系，捕捉智人谱系中的不同时间尺度。我们的工作证实并扩展了人类获得的胎儿脑组织中活跃的增强子与成年人测量的皮质表面积（包括与言语相关的左半球区域）之间的联系。该研究还表明，携带尼安德特人基因渗入变异的基因组区域对左半球钩束（参与将声音映射到意义的白质束）的连接性的贡献显着减弱。大脑大小和组织的变化代表了我们物种出现过程中一些最独特的变化。然而，对于人类进化过程中遗传因素如何导致神经解剖学改变的了解有限。在这里，我们分析了英国生物库中多达 30,000 人的神经影像和遗传数据，并整合了人类进化不同方面的基因组注释，包括基于古代 DNA 和比较基因组学的注释。我们表明，先前报道的最近皮质解剖学多基因选择的信号在更祖先同质的样本中是不可复制的。然后，我们研究进化注释与塑造每个半球皮质表面积和白质连接性的常见遗传变异之间的关系。我们的分析确定了人类获得的调节元件中的单核苷酸多态性遗传性富集，这些调节元件在早期大脑发育中活跃，影响皮质多个部分的表面区域，包括左半球言语相关区域。我们还检测到具有尼安德特人血统的基因组区域中钩束连接性的遗传力缺失；这是一条白质束，涉及记忆、语言和与神经精神疾病相关的社会情感处理。最后，我们发现与左半球三角部表面积相关的常见遗传位点与人类获得的增强子重叠，并影响 ZIC4（一种与神经发生有关的基因）的调节。这项工作展示了当今神经解剖学变异的基因组研究如何有助于揭示我们过去进化的复杂性。
Which aspects of our genetic makeup contribute to distinctly human features of brain anatomy? Here, we identify associations between common DNA variants and interindividual differences in cortical circuitry, based on neuroimaging in tens of thousands of people, and assess how they relate to genomic regions of evolutionary interest, capturing different timescales along the lineage leading to Homo sapiens. Our work confirms and extends links between human-gained enhancers active in fetal brain tissue and cortical surface area measured in adults, including left-hemisphere regions related to speech. The study also reveals that regions of the genome carrying introgressed Neanderthal variants make a significantly diminished contribution to connectivity of the left-hemisphere uncinate fasciculus, a white-matter tract involved in mapping sound to meaning. Alterations in brain size and organization represent some of the most distinctive changes in the emergence of our species. Yet, there is limited understanding of how genetic factors contributed to altered neuroanatomy during human evolution. Here, we analyze neuroimaging and genetic data from up to 30,000 people in the UK Biobank and integrate with genomic annotations for different aspects of human evolution, including those based on ancient DNA and comparative genomics. We show that previously reported signals of recent polygenic selection for cortical anatomy are not replicable in a more ancestrally homogeneous sample. We then investigate relationships between evolutionary annotations and common genetic variants shaping cortical surface area and white-matter connectivity for each hemisphere. Our analyses identify single-nucleotide polymorphism heritability enrichment in human-gained regulatory elements that are active in early brain development, affecting surface areas of several parts of the cortex, including left-hemispheric speech-associated regions. We also detect heritability depletion in genomic regions with Neanderthal ancestry for connectivity of the uncinate fasciculus; this is a white-matter tract involved in memory, language, and socioemotional processing with relevance to neuropsychiatric disorders. Finally, we show that common genetic loci associated with left-hemispheric pars triangularis surface area overlap with a human-gained enhancer and affect regulation of ZIC4, a gene implicated in neurogenesis. This work demonstrates how genomic investigations of present-day neuroanatomical variation can help shed light on the complexities of our evolutionary past.
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影响因子：
16.2
作者：
Geschwind DH;Rakic P
通讯作者：
Rakic P
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：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL