A common MECP2 haplotype associates with reduced cortical surface area in humans in two independent populations
A common MECP2 haplotype associates with reduced cortical surface area in humans in two independent populations
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DOI：
10.1073/pnas.0901866106
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发表时间：
2009-09-08
影响因子：
11.1
通讯作者：
Dale, Anders M.
中科院分区：
文献类型：
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作者：
Joyner, Alexander H.;Roddey, J. Cooper;Dale, Anders M.
基因MECP2是一个众所周知的大脑结构的决定因素。MECP2蛋白的突变导致微脑病，并与影响脑形态和认知的几种神经发育障碍有关。虽然MECP2突变导致严重的神经系统表型，但该遗传区域常见变异的影响尚不清楚。我们发现，MECP2及其周围区域中的常见序列变异与2个独立队列中的结构性脑大小测量相关，其中一个是来自主题性有组织精神病研究组的发现样本，另一个是来自阿尔茨海默病神经影像学倡议的复制样本。最具统计学显著性的重复关联（两个队列中P < 0.025）涉及SNP rs2239464的次要等位基因与皮质表面积减少，并且该发现在两个群体中均特异于男性性别。MECP2区域的变化与皮质表面积相关，但与皮质厚度无关。二次分析表明，该等位基因也与减少表面积在特定的皮质区域（楔，梭状回，部三角）在这两个群体。
The gene MECP2 is a well-known determinant of brain structure. Mutations in the MECP2 protein cause microencephalopathy and are associated with several neurodevelopmental disorders that affect both brain morphology and cognition. Although mutations in MECP2 result in severe neurological phenotypes, the effect of common variation in this genetic region is unknown. We find that common sequence variations in a region in and around MECP2 show association with structural brain size measures in 2 independent cohorts, a discovery sample from the Thematic Organized Psychosis research group, and a replication sample from the Alzheimer's Disease Neuroimaging Initiative. The most statistically significant replicated association (P < 0.025 in both cohorts) involved the minor allele of SNP rs2239464 with reduced cortical surface area, and the finding was specific to male gender in both populations. Variations in the MECP2 region were associated with cortical surface area but not cortical thickness. Secondary analysis showed that this allele was also associated with reduced surface area in specific cortical regions (cuneus, fusiform gyrus, pars triangularis) in both populations.