ABSTRACT

Specific reading disability (SRD) is defined by genetic and neural risk factors that are not fully understood. The current study used imaging genetics methodology to investigate relationships between SEMA6D, brain structure, and reading. SEMA6D, located on SRD risk locus DYX1, is involved in axon guidance, synapse formation, and dendrite development. SEMA6D’s associations with brain structure in reading-related regions of interest (ROIs) were investigated in a sample of children with a range of reading performance, from sites in Connecticut, CT (n = 67, 6–13 years, mean age = 9.07) and San Francisco, SF (n = 28, 5–8 years, mean age = 6.5). Multiple regression analyses revealed significant associations between SEMA6D’s rs16959669 and cortical thickness in the fusiform gyrus and rs4270119 and gyrification in the supramarginal gyrus in the CT sample, but this was not replicated in the SF sample. Significant clusters were not associated with reading. For white matter volume, combined analyses across both samples revealed associations between reading and the left transverse temporal gyrus, left pars triangularis, left cerebellum, and right cerebellum. White matter volume in the left transverse temporal gyrus was nominally related to rs1817178, rs12050859, and rs1898110 in SEMA6D, and rs1817178 was significantly related to reading. Haplotype analyses revealed significant associations between the whole gene and brain phenotypes. Results suggest SEMA6D likely has an impact on multiple reading-related neural structures, but only white matter volume in the transverse temporal gyrus was significantly related to reading in the current sample. As the sample was young, the transverse temporal gyrus, involved in auditory perception, may be more strongly involved in reading because phonological processing is still being learned. The relationship between SEMA6D and reading may change as different brain regions are involved during reading development. Future research should examine mediating effects, use additional brain measures, and use an older sample to better understand effects.

 抽象的

特定阅读障碍（SRD）是由尚未完全了解的遗传和神经风险因素定义的。当前的研究使用成像遗传学方法来研究SEMA6D 、大脑结构和阅读之间的关系。 SEMA6D位于 SRD 风险基因座 DYX1 上，参与轴突引导、突触形成和树突发育。 SEMA6D与阅读相关感兴趣区域 (ROI) 中大脑结构的关联在康涅狄格州康涅狄格州具有不同阅读表现的儿童样本中进行了调查（n = 67，6-13 岁，平均年龄 = 9.07）和旧金山旧金山（n = 28，5-8 岁，平均年龄 = 6.5）。多元回归分析揭示了 CT 样本中SEMA6D的 rs16959669 与梭状回的皮质厚度以及 rs4270119 与边缘上回的回旋之间存在显着关联，但这在 SF 样本中并未重复。显着的聚类与阅读无关。对于白质体积，对两个样本的综合分析揭示了阅读与左侧颞横回、左侧三角肌、左侧小脑和右侧小脑之间的关联。左侧颞横回的白质体积名义上与SEMA6D中的rs1817178、rs12050859和rs1898110相关，并且rs1817178与阅读显着相关。单倍型分析揭示了整个基因和大脑表型之间的显着关联。结果表明， SEMA6D可能对多个与阅读相关的神经结构产生影响，但在当前样本中，只有横颞回的白质体积与阅读显着相关。 由于样本还年轻，参与听觉感知的颞横回可能更强烈地参与阅读，因为语音处理仍在学习中。 SEMA6D和阅读之间的关系可能会随着阅读发展过程中涉及的不同大脑区域而改变。未来的研究应该检查中介效应，使用额外的大脑测量方法，并使用较旧的样本来更好地理解效应。