The folding of the human cerebral cortex is a highly genetically regulated process that allows for a much larger surface area to fit into the cranial vault and optimizes functional organization. Sulcal depth is a robust, yet understudied measure of localized folding, previously associated with a range of neurodevelopmental disorders. Here, we report the first genome-wide association study of sulcal depth. Through the Multivariate Omnibus Statistical Test (MOSTest) applied to vertex-wise measures from 33,748 participants of the UK Biobank (mean age 64.3 years, 52.0% female) we identified 856 genetic loci associated with sulcal depth at genome-wide significance (p=5x10-8). Comparison with two other measures of cortical morphology, cortical thickness and surface area, indicated that sulcal depth has higher yield in terms of loci discovered, higher heritability and higher effective sample size. There was a large amount of genetic overlap between the three traits, with gene-based analyses indicating strong associations with neurodevelopmental processes. Our findings demonstrate sulcal depth is a promising MRI phenotype that may enhance our understanding of human cortical morphology.

中文翻译：

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人类皮质折叠的遗传结构

人类大脑皮层的折叠是一个高度遗传调节的过程，可以使更大的表面积适合颅穹ault并优化功能组织。沟深是一种强有力的，但尚未被研究的局部折叠的量度，以前与一系列神经发育障碍有关。在这里，我们报告了首个全基因组的沟深度关联研究。通过对来自英国生物银行的33,748名参与者（平均年龄64.3岁，女性52.0％）进行顶点度量的多元综合统计测试（MOSTest），我们在全基因组意义上确定了856个与沟深相关的基因位点（p = 5x10 -8）。与其他两种皮质形态学指标（皮质厚度和表面积）进行比较后，发现在发现的基因座上，沟深具有较高的产量，更高的遗传力和更高的有效样本量。这三个性状之间存在大量的遗传重叠，基于基因的分析表明与神经发育过程密切相关。我们的研究结果表明，沟深是一种很有前途的MRI表型，可能会增强我们对人类皮层形态的了解。