Studies on the genetic and environmental basis of endometriosis

There is now considerable evidence that endometriosis is likely to be a complex multifactorial trait, such as diabetes or asthma, in which a number of susceptibility loci interact with each other, and the environment, to produce the disease phenotype. This thesis presents studies on the genetic and environmental basis of endometriosis in both a non-human primate model and in women. The study of the autopsy records of 399 female rhesus monkeys identified 81 (20%) with spontaneous endometriosis. Age, exposure to ≥ 3 oestradiol implants (relative risk 9.7, P < 0.001) or ≥ 1 hysterotomy (relative risk 5.8, P = 0.006) were significant risk factors as determined by conditional logistic regression. Living descendants of the affected animals had MRI scans which suggested that 8/113 (7%) had at least one endometriotic lesion >1 cm in diameter. Segregation analysis was conducted on the resulting 12 pedigrees, which contained 64 half sib-pairs, 2 full sibpairs and 11 mother-daughter pairs. Human, affected sib-pairs and families were recruited for the OXEGENE study to conduct sib-pair analysis using microsatellite markers at 10cM resolution across the entire genome. MRI studies of the first-degree relatives of women ... (continues)