Twin study of genetic and aging effects on X chromosome inactivation

Department of Medical Genetics,Rikshospitalet, Oslo, NorwayTo investigate the genetic influence on X chromosome inactivation and on age-related skewing of Xinactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118young monozygotic (MZ) twin pairs (18–53 years), 82 elderly MZ twin pairs (55–94 years), 146 youngdizygotic (DZ) twin pairs (20–54 years) and 112 elderly DZ twin pairs (64–95 years). Elderly twins had ahigher frequency of skewed X inactivation (34%) than young twins (15%) (Po0.001). Our data suggestthat the increase in skewing occurs after age 50–60 years. The intraclass correlation was 0.61 and 0.58 inyoung and elderly MZ twin pairs, and 0.08 and 0.09 in young and elderly DZ twin pairs. Biometric analysisshowed that dominant genetic effects accounted for 63 and 58% of the variance of XIP in the young andelderly twin pairs, respectively. The dominant genetic effect and the shared environment formonochorionic MZ twins may explain the high intraclass correlation for the MZ twin pairs compared to theDZ twin pairs. We did not observe a significant decrease in the intraclass correlation in elderly MZ twinscompared to young MZ twins, which would be expected if age-related skewing were due to stochasticfactors. We conclude that the increased skewing with age implies that a genetically dependent selection ofblood cells take place.European Journal of Human Genetics (2005) 13, 599–606. doi:10.1038/sj.ejhg.5201398Published online 9 March 2005Keywords: X chromosome; X inactivation; twins; elderlyIntroduction