美国国家心理健康研究所Armin Raznahan课题组揭示X染色体对人类神经解剖学变异的影响。相关论文于2021年7月22日在线发表在《自然—神经科学》杂志上。

　　据研究人员介绍，长期以来，人们假设X染色体对大脑有不成比例的影响，因为它富含在大脑中表达的基因，并与智力障碍有关。

　　通过对英国生物库中32256名个体的X染色体对人脑解剖的影响（XIs）进行分区遗传性分析，研究人员验证了这一假说。研究人员首先建立了X染色体对脑解剖学影响的剂量补偿证据：反映出男性的X染色体比女性大，这与神经解剖学变异中的区域性别差异相关。在影响注意力、决策和运动控制的皮层系统的相对表面积方面，XIs明显大于从X染色体大小所预测的。后续的关联分析表明，X连锁基因对认知具有多种影响。

　　这项研究揭示了X染色体在人类神经发育中的特殊作用，并敦促在未来的全基因组关联研究中更多地纳入该染色体。

　　附：英文原文

　　Title: X-chromosome influences on neuroanatomical variation in humans

　　Author: Travis T. Mallard, Siyuan Liu, Jakob Seidlitz, Zhiwei Ma, Dustin Moraczewski, Adam Thomas, Armin Raznahan

　　Issue&Volume: 2021-07-22

　　Abstract: The X-chromosome has long been hypothesized to have a disproportionate influence on the brain based on its enrichment for genes that are expressed in the brain and associated with intellectual disability. Here, we verify this hypothesis through partitioned heritability analysis of X-chromosome influences (XIs) on human brain anatomy in 32,256 individuals from the UK Biobank. We first establish evidence for dosage compensation in XIs on brain anatomy—reflecting larger XIs in males compared to females, which correlate with regional sex-biases in neuroanatomical variance. XIs are significantly larger than would be predicted from X-chromosome size for the relative surface area of cortical systems supporting attention, decision-making and motor control. Follow-up association analyses implicate X-linked genes with pleiotropic effects on cognition. Our study reveals a privileged role for the X-chromosome in human neurodevelopment and urges greater inclusion of this chromosome in future genome-wide association studies.