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皮质折叠的遗传性:来自人类连接组计划的证据。

The Heritability of Cortical Folding: Evidence from the Human Connectome Project.

机构信息

Departments of Radiology and Psychiatry, Division of Neuroradiology, Brain Behavior Laboratory, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

Section on Developmental Neurogenomics, National Institute of Mental Health, Bethesda, MD 20892, USA.

出版信息

Cereb Cortex. 2021 Jan 1;31(1):702-715. doi: 10.1093/cercor/bhaa254.

Abstract

The mechanisms underlying cortical folding are incompletely understood. Prior studies have suggested that individual differences in sulcal depth are genetically mediated, with deeper and ontologically older sulci more heritable than others. In this study, we examine FreeSurfer-derived estimates of average convexity and mean curvature as proxy measures of cortical folding patterns using a large (N = 1096) genetically informative young adult subsample of the Human Connectome Project. Both measures were significantly heritable near major sulci and primary fissures, where approximately half of individual differences could be attributed to genetic factors. Genetic influences near higher order gyri and sulci were substantially lower and largely nonsignificant. Spatial permutation analysis found that heritability patterns were significantly anticorrelated to maps of evolutionary and neurodevelopmental expansion. We also found strong phenotypic correlations between average convexity, curvature, and several common surface metrics (cortical thickness, surface area, and cortical myelination). However, quantitative genetic models suggest that correlations between these metrics are largely driven by nongenetic factors. These findings not only further our understanding of the neurobiology of gyrification, but have pragmatic implications for the interpretation of heritability maps based on automated surface-based measurements.

摘要

脑回形成的机制尚不完全清楚。先前的研究表明,脑沟深度的个体差异与遗传有关,与其他脑沟相比,更深和更原始的脑沟具有更高的遗传性。在这项研究中,我们使用人类连接组计划中一个大型(N=1096)具有遗传信息的年轻成年子样本,使用基于 FreeSurfer 的平均凸度和平均曲率估计值作为皮质折叠模式的替代测量指标。这两个指标在主要脑沟和初级裂附近具有显著的遗传性,其中大约一半的个体差异可以归因于遗传因素。在更高阶脑回和脑沟附近的遗传影响要低得多,且大部分不显著。空间置换分析发现,遗传模式与进化和神经发育扩张的图谱显著负相关。我们还发现平均凸度、曲率和几个常见的表面指标(皮质厚度、表面积和皮质髓鞘化)之间存在很强的表型相关性。然而,定量遗传模型表明,这些指标之间的相关性主要是由非遗传因素驱动的。这些发现不仅进一步加深了我们对脑回形成的神经生物学的理解,而且对基于自动表面测量的遗传图谱的解释具有实际意义。

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