October 18, 2012

Epigenetics and IQ variability

A new study on monozygotic (identical) twins with clear IQ differences finds that epigenetic methylation of certain genes may be the cause:

Chih-Chieh Yu, Genome-Wide DNA Methylation and Gene Expression Analyses of Monozygotic Twins Discordant for Intelligence Levels. PLoS ONE, 2012. Open access ··> LINK [doi:10.1371/journal.pone.0047081]


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.

The list of genes with a detectable effect is as follows:

Table 2. List of genes having the same tendency of expression level in most twin pairs.

It's worth noticing that a recent study (Chabris 2012) reviewing the literature found that most or maybe even all alleged genetic influences in intelligence are probably false positives (discussed here). Therefore is probable that many (most?, all?) differences in intelligence are caused by environmental influences, often manifested in epigenetic modifications like the ones detected in this study.

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