title: Skewed X inactivation and survival: a 13-year follow-up study of elderly twins and singletons.
abstract: In mammalian females, one of the two X chromosomes is inactivated in early embryonic life. Females are therefore mosaics for two cell populations, one with the maternal and one with the paternal X as the active X chromosome. A skewed X inactivation is a marked deviation from a 50:50 ratio. In populations of women past 55-60 years of age, an increased degree of skewing (DS) is found. Here the association between age-related skewing and mortality is analyzed in a 13-year follow-up study of 500 women from three cohorts (73-100 years of age at intake). Women with low DS had significantly higher mortality than the majority of women who had a more skewed DS (hazard ratio: 1.30; 95% CI: 1.04-1.64). The association between X inactivation and mortality was replicated in dizygotic twin pairs for which the co-twin with the lowest DS also had a statistically significant tendency to die first in the twin pairs with the highest intra-pair differences in DS (proportion: 0.71; 95% CI: 0.52-0.86). Both results suggest that lower DS is associated with higher mortality. We therefore propose that age-related skewing may be partly due to a population selection with lower mortality among those with higher DS.
authors.affiliation: Epidemiology Unit, The Danish Aging Research Center, Institute of Public Health, University of Southern Denmark, Odense, Denmark. jmengel-from@health.sdu.dk
authors.forename: Jonas
authors.initials: J
authors.lastname: Mengel-From
authors.forename: Mikael
authors.initials: M
authors.lastname: Thinggaard
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.forename: James W
authors.initials: JW
authors.lastname: Vaupel
authors.forename: Karen Helene
authors.initials: KH
authors.lastname: Orstavik
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008136:Longevity / Q000235:genetics*; D009026:Mortality; D049951:X Chromosome Inactivation / Q000235:genetics*