GENETIC EPIDEMIOLOGY OF ENDOMETRIOSIS

University Of Wisconsin-Madison, Madison WI

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To investigate the genetic epidemiology of endometriosis. While the cause remains unknown, there is a clear familial aggregation of endometriosis in both humans and non-human primates. In the proposed project, a multigenerational pedigree of rhesus monkeys demonstrating spontaneous disease with identical morphology and histology to that seen in women will serve as the animal model for genetic studies. This data will be coupled with the specimens and electronic medical records of patients previously diagnosed with endometriosis to verify genetic markers identified in the monkey pedigree. The pedigree was updated and refined by Kirsten Geraedts. The five specific aims of the project are to: 1) Confirm the diagnosis of endometriosis in 937 women with electronic diagnoses of endometriosis enrolled in the Personalized Medicine Research Project (PMRP). This is the largest population-based DNA biobank in the United States;it allows population-based estimates of allele frequencies and genetic associations. 2) Recruit additional women with surgically confirmed endometriosis into the PMRP cohort to reach a target of 1000 cases. 3) Administer validated endometriosis quality of life questionnaires to the women with confirmed endometriosis and document self-reported family history of endometriosis. 4) Quantify known risk factors (age, smoking history, physical activity, family history of endometriosis, endocrine factors), treatments (medical and surgical), and known outcomes (cancers, reduced fertility) in women with endometriosis. 5) Describe the genetic epidemiology of endometriosis in this cohort using the information collected in Aim 1. The Primate Center has a long history of investigating the prevalence and familial aggregation of endometriosis in rhesus macaques. Between 1978 and 2002, WNPRC researchers identified 144 rhesus macaques with endometriosis. They established a large multigenerational pedigree and nine nuclear families comprising 1,602 females. They found that the prevalence of endometriosis increased with age. In addition, they saw a higher recurrence risk for full siblings when compared to maternal half siblings and paternal half sibs. Those studies were led by Stephen Kennedy, head of the Nuffield Department of Obstetrics and Gynecology at Oxford University, and Joe Kemnitz, WNRPC director and professor of physiology. They focused on the mode of inheritance, location of potential genetic susceptibility loci, and the influence of environmental factors on disease risk. Ricki Colman, now a WNPRC associate scientist, conducted the non-invasive imaging studies at the time. The Marshfield Clinic collaboration continues this evaluation of pedigree and genetic information. The project is also expanding to include a web-based survey of the prevalence of endometriosis in the colonies of the other National Primate Research Centers. This project uses WNPRC Animal Services and Research Services. PUBLICATION: Lin J, Kennedy SH, Svarovsky T, Rogers J, Kemnitz JW, Xu A, Zondervan KT. High-quality genomic DNA extraction from formalin-fixed and paraffin-embedded samples deparaffinized using mineral oil. Anal Biochem. 2009 Dec 15;395(2):265-7. Epub 2009 Aug 19.