1. ¹Faculty Division, Rikshospitalet, University of Oslo, Norway
2. ²The Danish Twin Registry, Section for Epidemiology, University of Southern Denmark, Odense, Denmark
3. ³Department of Obstetrics and Gynecology and Human Genetics, The Research Institute of the McGill University Health Center, McGill University, Montreal, Canada
4. ⁴Danish Epidemiology Science Centre, Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark
5. ⁵Medical Department C, Odense University Hospital, Odense, Denmark
6. ⁶Department of Medical Genetics, Rikshospitalet, Oslo, Norway

Correspondence: Professor KH Ørstavik, Department of Medical Genetics, Rikshospitalet, Forskningsveien 2b, Oslo, Norway. Tel: +47 23075588; Fax: +47 23075590; E-mail: k.h.orstavik@medisin.uio.no

Received 20 October 2004; Revised 14 January 2005; Accepted 26 January 2005; Published online 9 March 2005.

Abstract

To investigate the genetic influence on X chromosome inactivation and on age-related skewing of X inactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118 young monozygotic (MZ) twin pairs (18–53 years), 82 elderly MZ twin pairs (55–94 years), 146 young dizygotic (DZ) twin pairs (20–54 years) and 112 elderly DZ twin pairs (64–95 years). Elderly twins had a higher frequency of skewed X inactivation (34%) than young twins (15%) (P<0.001). Our data suggest that the increase in skewing occurs after age 50–60 years. The intraclass correlation was 0.61 and 0.58 in young and elderly MZ twin pairs, and 0.08 and 0.09 in young and elderly DZ twin pairs. Biometric analysis showed that dominant genetic effects accounted for 63 and 58% of the variance of XIP in the young and elderly twin pairs, respectively. The dominant genetic effect and the shared environment for monochorionic MZ twins may explain the high intraclass correlation for the MZ twin pairs compared to the DZ twin pairs. We did not observe a significant decrease in the intraclass correlation in elderly MZ twins compared to young MZ twins, which would be expected if age-related skewing were due to stochastic factors. We conclude that the increased skewing with age implies that a genetically dependent selection of blood cells take place.