Background

The functional significance and mechanisms determining the development and individual variability of structural brain asymmetry remain unclear. Here, we systematically analyzed all relevant components of the most prominent structural asymmetry, brain torque (BT), and their relationships with potential genetic and nongenetic modifiers in a sample comprising 24,112 individuals from six cohorts.

Methods

BT features, including petalia, bending, dorsoventral shift, brain tissue distribution asymmetries, and cortical surface positional asymmetries, were directly modeled using a set of automatic three-dimensional brain shape analysis approaches. Age-, sex-, and handedness-related effects on BT were assessed. The genetic architecture and phenomic associations of BT were investigated using genome- and phenome-wide association scans.

Results

Our results confirmed the population-level predominance of the typical counterclockwise torque and suggested a first attenuating, then enlarging dynamic across the life span (3–81 years) primarily for frontal, occipital, and perisylvian BT features. Sex/handedness, BT, and cognitive function of verbal-numerical reasoning were found to be interrelated statistically. We observed differential heritability of up to 56% for BT, especially in temporal language areas. Individual variations of BT were also associated with various phenotypic variables of neuroanatomy, cognition, lifestyle, sociodemographics, anthropometry, physical health, and adult and child mental health. Our genomic analyses identified a number of genetic associations at lenient significance levels, which need to be further validated using larger samples in the future.

Conclusions

This study provides a comprehensive description of BT and insights into biological and other factors that may contribute to the development and individual variations of BT.

中文翻译：

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在 24,112 个个体中绘制复杂的脑力矩成分及其遗传结构和表型关联

背景

决定脑结构不对称的发展和个体变异性的功能意义和机制仍不清楚。在这里，我们系统地分析了样本中最突出的结构不对称、脑扭矩 (BT) 的所有相关成分，以及它们与潜在遗传和非遗传修饰因子的关系，该样本包含来自六个队列的 24,112 人。

方法

BT 特征，包括花瓣、弯曲、背腹侧移位、脑组织分布不对称和皮质表面位置不对称，使用一组自动三维脑形状分析方法直接建模。评估了年龄、性别和用手习惯对 BT 的影响。使用全基因组和全表型关联扫描研究了 BT 的遗传结构和表型关联。

结果

我们的结果证实了典型的逆时针扭矩在人口水平上占主导地位，并建议在整个生命周期（3-81 岁）内首先衰减，然后扩大动态，主要针对额叶、枕叶和外侧裂 BT 特征。发现性别/惯用手、BT 和语言数字推理的认知功能在统计学上相互关联。我们观察到 BT 的差异遗传力高达 56%，尤其是在时间语言区域。BT 的个体差异还与神经解剖学、认知、生活方式、社会人口学、人体测量学、身体健康以及成人和儿童心理健康的各种表型变量相关。我们的基因组分析确定了许多显着性水平较低的遗传关联，未来需要使用更大的样本进一步验证。

结论

本研究提供了对 BT 的全面描述以及对可能导致 BT 的发展和个体变异的生物学和其他因素的见解。