This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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. A manuscript is in submission.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000167-50
Application #
8358225
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$28,120
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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