Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.
Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.
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DOI：
10.1371/journal.pone.0047081
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Toda T
中科院分区：
文献类型：
--
作者：
Yu CC;Furukawa M;Kobayashi K;Shikishima C;Cha PC;Sese J;Sugawara H;Iwamoto K;Kato T;Ando J;Toda T
通过智商(IQ)测试衡量的人类智力，在人类数量性状中表现出最高的遗传力之一。然而，由于单个基因的影响范围很小，识别与智力有关的数量性状基因的研究面临着挑战。表型不一致的同卵双胞胎提供了一种可行的方法来最大限度地减少无关遗传和环境因素的影响，并通过发现双胞胎之间的表观遗传或基因表达差异而产生更可解释的结果。在这里，我们进行了基于阵列的全基因组DNA甲基化和基因表达分析，使用了17对智能不一致的健康MZ双胞胎。与Rho GTPase相关的ARHGAP18基因在两两甲基化状态分析中被鉴定，并通过直接亚硫酸氢盐测序和定量RT-PCR验证。为了进行表达谱分析，高智商双胞胎组与其同卵双胞胎组之间的基因集浓缩分析(GSEA)显示，高智商组中几个核糖体相关基因和DNA复制相关基因的表达上调。为了更多地关注个体对，我们进行了成对的GSEA和前沿分析，这表明在智商较低的双胞胎中，几个离子通道相关基因的表达上调。我们的发现暗示，这些基因组可能与智商有关，应该会揭示人类智力的潜在机制。
Human intelligence, as measured by intelligence quotient (IQ) tests, demonstrates one of the highest heritabilities among human quantitative traits. Nevertheless, studies to identify quantitative trait loci responsible for intelligence face challenges because of the small effect sizes of individual genes. Phenotypically discordant monozygotic (MZ) twins provide a feasible way to minimize the effects of irrelevant genetic and environmental factors, and should yield more interpretable results by finding epigenetic or gene expression differences between twins. Here we conducted array-based genome-wide DNA methylation and gene expression analyses using 17 pairs of healthy MZ twins discordant intelligently. ARHGAP18, related to Rho GTPase, was identified in pair-wise methylation status analysis and validated via direct bisulfite sequencing and quantitative RT-PCR. To perform expression profile analysis, gene set enrichment analysis (GSEA) between the groups of twins with higher IQ and their co-twins revealed up-regulated expression of several ribosome-related genes and DNA replication-related genes in the group with higher IQ. To focus more on individual pairs, we conducted pair-wise GSEA and leading edge analysis, which indicated up-regulated expression of several ion channel-related genes in twins with lower IQ. Our findings implied that these groups of genes may be related to IQ and should shed light on the mechanism underlying human intelligence.
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影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
影响因子：
64.8
作者：
Deary, Ian J.;Yang, Jian;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
影响因子：
9.9
作者：
Biousse, V;Brown, MD;Wallace, DC
通讯作者：
Wallace, DC
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M