Genome-wide DNA methylation and gene expression analyses of monozygotic twins discordant for intelligence levels.
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.
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe University, Kobe, Japan.
Chih-Chieh
CC
Yu
Mari
M
Furukawa
Kazuhiro
K
Kobayashi
Chizuru
C
Shikishima
Pei-Chieng
PC
Cha
Jun
J
Sese
Hiroko
H
Sugawara
Kazuya
K
Iwamoto
Tadafumi
T
Kato
Juko
J
Ando
Tatsushi
T
Toda
D000328:Adult; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014430:Twins, Monozygotic / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
C542464:ARHGAP18 protein, human; D020690:GTPase-Activating Proteins