Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels

Chih Chieh Yu, Mari Furukawa, Kazuhiro Kobayashi, Chizuru Shikishima, Pei Chieng Cha, Jun Sese, Hiroko Sugawara, Kazuya Iwamoto, Tadafumi Kato, Juko Ando, Tatsushi Toda

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere47081
JournalPloS one
Volume7
Issue number10
DOIs
Publication statusPublished - 2012 Oct 17

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yu, C. C., Furukawa, M., Kobayashi, K., Shikishima, C., Cha, P. C., Sese, J., Sugawara, H., Iwamoto, K., Kato, T., Ando, J., & Toda, T. (2012). Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels. PloS one, 7(10), [e47081]. https://doi.org/10.1371/journal.pone.0047081