Genetic overlap between endometriosis and endometrial cancer: evidence from cross‐disease genetic correlation and GWAS meta‐analyses
Abstract
Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 02, 2018
- Source ID
- 10.1002/cam4.1445
Entities
People
- Adriaan Vanderstichele
- Alexander Hein
- Alfons Meindl
- Alison Dunning
- Amanda Spurdle
- Andrew P. Morris
- Angela Cox
- Angela Jones
- Anjali K. Henders
- Annika Lindblom
- Anthony Swerdlow
- Arif B. Ekici
- Barbara Burwinkel
- Camilla Krakstad
- Catherine S. Healey
- Dale R. Nyholt
- Daniela Annibali
- Deborah J. Thompson
- Diether Lambrechts
- Douglas F. Easton
- Elizabeth G. Holliday
- Ellen L Goode
- Emma Tham
- Erling Hoivik
- Fergus J. Couch
- Frederic Amant
- Geoffrey Otton
- Graham Giles
- Grant W. Montgomery
- Henrica M. J. Werner
- Hermann Brenner
- Hiltrud Brauch
- Ian Tomlinson
- Ingo Runnebaum
- Jenny Chang‐claude
- Jeroen Depreeuw
- Jodie N Painter
- Joe Dennis
- John Attia
- John L. Hopper
- Jonathan P Tyrer
- Jone Trovik
- Julian Peto
- Julie M. Cunningham
- Kamila Czene
- Katie Ashton
- Krina T. Zondervan
- Kyriaki Michailidou
- Lynn B. Martin
- Maggie Gorman
- Manjeet K. Bolla
- Mark Mcevoy
- Matthias Dürst
- Matthias Rübner
- Matthias W. Beckmann
- Miriam Mints
- Mitul Shah
- Nicholas G. Martin
- Paul D P Pharoah
- Penelope M. Webb
- Per Hall
- Peter A. Fasching
- Peter Hillemanns
- Qin Wang
- Rodney J. Scott
- Scott Gordon
- Sean C. Dowdy
- Shahana Ahmed
- Shirley Hodson
- Stacey J Winham
- Stuart Macgregor
- Thilo Dörk
- Timothy H. T. Cheng
- Tony Proietto
- Tracy A. O'mara
- Vessela N. Kristensen
Organizations
- Agency for Science, Technology and Research
- Australian Research Council
- Canadian Institutes of Health Research
- Cancer Council New South Wales
- Cancer Council Queensland
- Cancer Council SA
- Cancer Council Tasmania
- Cancer Council Victoria
- Cancer Research UK
- Flanders Institute for Biotechnology
- Friedrich Schiller University Jena
- Friedrich-Alexander-Universität Erlangen-Nürnberg
- German Cancer Research Center
- Hannover Medical School
- Haukeland University Hospital
- Heidelberg University
- Hunter Medical Research Institute
- Institute of Cancer Research
- John Hunter Hospital
- Karolinska Institutet
- Katholieke Universiteit Leuven
- London School of Hygiene & Tropical Medicine
- Mayo Clinic
- Mayo Foundation for Medical Education and Research
- Medical Research Council
- National Health and Medical Research Council
- National Institutes of Health
- Norwegian Cancer Society
- Nuffield College
- Oslo University Hospital
- Ovarian Cancer Australia
- Ovarian Cancer Research Alliance
- QIMR Berghofer Medical Research Institute
- Queensland University of Technology
- Research Council of Norway
- Swedish Cancer Society
- Technical University of Munich
- The Breast Cancer Research Foundation
- United States Army Medical Research and Development Command
- United States Department of Defense
- University of Bergen
- University of California, Los Angeles
- University of Cambridge
- University of Liverpool
- University of London
- University of Melbourne
- University of Newcastle
- University of Oslo
- University of Oxford
- University of Queensland
- University of Sheffield
- University of Tübingen
- Wellcome Trust
- Western Norway Regional Health Authority