No major role for X-inactivation in variations of intelligence and behavioral problems at middle childhood

Although members of monozygotic (MZ) twin pairs are identical in genomic sequence, epigenetic mechanisms may occasion difference in gene expression and, consequently, twin discordance in complex traits. Recent work suggests that the epigenetic process of X-inactivation in female individuals may impact on intelligence and child behavioral problems. The timing of X-inactivation has been linked to chorionic splitting in MZ twins. Dichorionic monozygotic (DC-MZ) twinning, unlike monochorionic monozygotic (MC-MZ) twinning, occurs prior to the time of X-inactivation in female organisms. Therefore, the hypothesis of a causal role of X-inactivation in intelligence and behavioral problems can be analyzed by modeling the statistical interaction between sex and chorion type for within-pair differences in these traits in MZ twins. In this study, the effect of X-inactivation on childhood behavioral problems, measured with the CBCL, was studied in a sample of 324 MZ twin pairs from the EFPTS and the effect of X-inactivation on IQ was studied in a sample of 272 twin pairs from the same twin survey. Information on chorion type, gestational age, and birth weight was additionally collated. No significant statistical interaction was found between sex and chorion type, indicating that X-inactivation is not likely involved in variations in intelligence or behavioral problems in middle childhood. Further studies are required to replicate these findings and may explore the role of X-inactivation at different ages or at the extreme scores in the spectrum of intelligence and behavioral problems or may focus on other epigenetic mechanisms.