Genetic factors contribute to the risk of developing endometriosis
Abstract
BACKGROUND: Endometriosis is known to cluster within nuclear families. The extent of familial clustering can be evaluated in Iceland with its large population-based genealogical database. METHODS AND RESULTS: Applying several measures of familiality we demonstrated that 750 women with endometriosis were significantly more interrelated than matched control groups. The risk ratio for sisters was 5.20 (P < 0.001) and for cousins 1.56 (P = 0.003). The average kinship coefficient for the patients was significantly higher than that calculated for 1000 sets of 750 matched controls (P < 0.001) and this remained significant when contribution from first-degree relatives was excluded (P < 0.05). The minimum number of ancestors required to account for the group of patients was compared with the minimum number of ancestors required to account for the control groups at different time points in the past. The minimum number of founders for the group of patients was significantly smaller than for the control groups. Affected cousin pairs were as likely to be paternally connected as maternally connected. CONCLUSIONS: This is the first population-based study using an extensive genealogy database to examine the genetic contribution to endometriosis. A genetic factor is present, with a raised risk in close and more distant relatives, and a definite kinship factor with maternal and paternal inheritance contributing.
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Studies in Australian twins, the Icelandic population, and rhesus macaques provide strong evidence for a genetic contribution to endometriosis, with heritability estimated to be around 50%.
“However, studies in Australian twins, 45 in the Icelandic population, 43 and in rhesus macaques 49 provide strong evidence for a genetic contribution to the disease with the heritability of endometriosis estimated to be around 50%. 45”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [43]
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Cites
The American Journal of Human Genetics
S., J. (1950) · Population · doi:10.2307/1523704 · Cited by 5,124 · see citing works
Revised American Fertility Society Classification of Endometriosis: 1985
(1985) · Fertility and Sterility · doi:10.1016/s0015-0282(16)48430-x · Cited by 1,803 · see citing works
Linkage strategies for genetically complex traits. I. Multilocus models.
RISCH, N. J. (1990) · PubMed · Cited by 1,315 · see citing works
Olive, D. L., & Schwartz, L. B. (1993) · New England Journal of Medicine · doi:10.1056/nejm199306173282407 · Cited by 675 · see citing works
Heritable aspects of endometriosis
Simpson, J. L., Elias, S., Malinak, L. R., & Buttram, V. C. (1980) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(80)90917-5 · Cited by 468 · see citing works
Mathematical and Statistical Methods for Genetic Analysis
Lange, K. L. (2002) · Statistics in the health sciences · doi:10.1007/978-0-387-21750-5 · Cited by 463 · see citing works
Genetic influences on endometriosis in an Australian twin sample
Treloar, S. A., O’Connor, D. T., O’Connor, V. M., & Martin, N. G. (1999) · Fertility and Sterility · doi:10.1016/s0015-0282(98)00540-8 · Cited by 353 · see citing works
Goldfarb, A. F. (1970) · Fertility and Sterility · doi:10.1016/s0015-0282(16)37275-2 · Cited by 279 · see citing works
The familial risk of endometriosis
Moen, M. H., & Magnus, P. (1993) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.3109/00016349309058164 · Cited by 248 · see citing works
Inheritance of human longevity in Iceland
Gudmundsson, H., Gudbjartsson, D. F., Kong, A., Guðbjartsson, H., Frigge, M., Gulcher, J. R., & Stefánsson, K. (2000) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200527 · Cited by 231 · see citing works
Self-citationEndometriosis in monozygotic twins
Hadfield, R. M., Mardon, H. J., Barlow, D. H., & Kennedy, S. H. (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)00359-2 · Cited by 166 · see citing works
Kennedy, S., Mardon, H., & Barlow, D. (1995) · Journal of Assisted Reproduction and Genetics · doi:10.1007/bf02214126 · Cited by 157 · see citing works
Epidemiology of endometriosis in a Norwegian county
Moen, M. H., & Schei, B. (1997) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.3109/00016349709024584 · Cited by 154 · see citing works
Protection of privacy by third-party encryption in genetic research in Iceland
Gulcher, J. R., Kristjánsson, K., Guðbjartsson, H., & Stefánsson, K. (2000) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200530 · Cited by 138 · see citing works
Self-citationEndometriosis in monozygotic twins
Moen, M. H. (1994) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.3109/00016349409013396 · Cited by 114 · see citing works
Kennedy, S. (1999) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(98)00213-9 · Cited by 110 · see citing works
Family trait analysis: A case-control study of 43 women with endometriosis and their best friends
Lamb, K., Hoffmann, R. G., & Nichols, T. R. (1986) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(86)90608-3 · Cited by 98 · see citing works
Familial inheritance of endometriosis in a British population. A case control study
Coxhead, D., & Thomas, E. J. (1993) · Journal of Obstetrics and Gynaecology · doi:10.3109/01443619309151773 · Cited by 97 · see citing works
Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study
Hadfield, R. (1997) · Human Reproduction Update · doi:10.1093/humupd/3.2.109 · Cited by 86 · see citing works
The familial nature of multiple sclerosis
Sadovnick, A. D., & MacLeod, P. (1981) · Neurology · doi:10.1212/wnl.31.8.1039 · Cited by 55 · see citing works
Familial risk among patients with endometriosis
Dos Reis, R. M., Silva De Sá, M. F., De Moura, M. D., Nogueira, A. A., Ribeiro, J. U., Ramos, E. S., & Ferriani, R. A. (1999) · Journal of Assisted Reproduction and Genetics · doi:10.1023/a:1020559201968 · Cited by 48 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Giudice, L. C., & Kao, L. C. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17403-5 · Cited by 3,166 · see citing works
Endometriosis: pathogenesis and treatment
Vercellini, P., Viganò, P., Somigliana, E., & Fedele, L. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.255 · Cited by 1,940 · see citing works
Rethinking mechanisms, diagnosis and management of endometriosis
Chapron, C., Marcellin, L., Borghese, B., & Santulli, P. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0245-z · Cited by 1,084 · see citing works
<i>Stem Cells and the Pathogenesis of Endometriosis</i>
Sasson, I. E., & Taylor, H. S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1434.014 · Cited by 371 · see citing works
Priorities for Endometriosis Research: Recommendations From an International Consensus Workshop
Rogers, P. A. W., D’Hooghe, T. M., Fazleabas, A., Gargett, C. E., Giudice, L. C., Montgomery, G. W., Rombauts, L., Salamonsen, L. A., & Zondervan, K. T. (2009) · Reproductive Sciences · doi:10.1177/1933719108330568 · Cited by 346 · see citing works
Incidence of endometriosis by study population and diagnostic method: the ENDO study
Buck Louis, G. M., Hediger, M. L., Peterson, C. M., Croughan, M., Sundaram, R., Stanford, J., Chen, Z., Fujimoto, V. Y., Varner, M. W., Trumble, A., et al. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.05.087 · Cited by 309 · see citing works
Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis
Painter, J. N., Anderson, C. A., Nyholt, D. R., Macgregor, S., Lin, J., Lee, S. H., Lambert, A., Zhao, Z. Z., Roseman, F., Guo, Q., et al. (2011) · Nature Genetics · doi:10.1038/ng.731 · Cited by 308 · see citing works
Endometriosis: The Role of Neuroangiogenesis
Asante, A., & Taylor, R. N. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142158 · Cited by 223 · see citing works
Saha, R., Pettersson, H. J., Svedberg, P., Olovsson, M., Bergqvist, A., Marions, L., Tornvall, P., & Kuja-Halkola, R. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.06.035 · Cited by 211 · see citing works
The search for genes contributing to endometriosis risk
Montgomery, G. W., Nyholt, D. R., Zhao, Z. Z., Treloar, S. A., Painter, J. N., Missmer, S. A., Kennedy, S. H., & Zondervan, K. T. (2008) · Human Reproduction Update · doi:10.1093/humupd/dmn016 · Cited by 211 · see citing works
Genome-Wide Association Study Link Novel Loci to Endometriosis
Albertsen, H. M., Chettier, R., Farrington, P., & Ward, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058257 · Cited by 161 · see citing works
Rogers, P. A. W., D’Hooghe, T. M., Fazleabas, A., Giudice, L. C., Montgomery, G. W., Petraglia, F., & Taylor, R. N. (2013) · Reproductive Sciences · doi:10.1177/1933719113477495 · Cited by 154 · see citing works
Adachi, S., Tajima, A., Quan, J., Haino, K., Yoshihara, K., Masuzaki, H., Katabuchi, H., Ikuma, K., Suginami, H., Nishida, N., et al. (2010) · Journal of Human Genetics · doi:10.1038/jhg.2010.118 · Cited by 103 · see citing works
Familial aggregation of endometriosis in a large pedigree of rhesus macaques
Zondervan, K. T. (2004) · Human Reproduction · doi:10.1093/humrep/deh052 · Cited by 99 · see citing works
Borghese, B., Barbaux, S., Mondon, F., Santulli, P., Pierre, G., Vinci, G., Chapron, C., & Vaiman, D. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0160 · Cited by 97 · see citing works
Polymorphisms and endometriosis: A systematic review and meta-analyses
Méar, L., Herr, M., Fauconnier, A., Pineau, C., & Vialard, F. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmz034 · Cited by 85 · see citing works
Simpson, J. L., Bischoff, F. Z., Kamat, A., Buster, J. E., & Carson, S. A. (2003) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/s0889-8545(02)00051-7 · Cited by 83 · see citing works
The role of gene polymorphisms in endometriosis
Matalliotakis, M., Zervou, M. I., Matalliotaki, C., Rahmioglu, N., Koumantakis, G., Kalogiannidis, I., Prapas, I., Zondervan, K., Spandidos, D. A., Matalliotakis, I., et al. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7398 · Cited by 75 · see citing works
Insights into assessing the genetics of endometriosis
Rahmioglu, N., Missmer, S. A., Montgomery, G. W., & Zondervan, K. T. (2012) · Current Obstetrics and Gynecology Reports · doi:10.1007/s13669-012-0016-5 · Cited by 71 · see citing works
Genetics of endometriosis: current status and prospects
Vigano, P. (2007) · Frontiers in Bioscience · doi:10.2741/2308 · Cited by 62 · see citing works
Monsivais, D., Dyson, M. T., Yin, P., Navarro, A., Coon, J. S., Pavone, M. E., & Bulun, S. E. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.01.012 · Cited by 62 · see citing works
Genetics of endometriosis: heritability and candidate genes
Bischoff, F., & Simpson, J. L. (2004) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2004.01.004 · Cited by 57 · see citing works
Endometriosis, dysmenorrhea and diet—What is the evidence?
Fjerbæk, A., & Knudsen, U. B. (2007) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2006.12.006 · Cited by 53 · see citing works
Candidate genes for age at menarche are associated with endometriosis
Ponomarenko, I., Reshetnikov, E., Polonikov, A., Verzilina, I., Sorokina, I., Elgaeva, E. E., Tsepilov, Y. A., Yermachenko, A., Dvornyk, V., & Churnosov, M. (2020) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2020.04.016 · Cited by 49 · see citing works
Should genetics now be considered the pre-eminent etiologic factor in endometriosis?
Montgomery, G. W., Mortlock, S., & Giudice, L. C. (2020) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2019.10.020 · Cited by 49 · see citing works
Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis
Steinthorsdottir, V., Thorleifsson, G., Aradottir, K., Feenstra, B., Sigurdsson, A., Stefansdottir, L., Kristinsdottir, A. M., Zink, F., Halldorsson, G. H., Munk Nielsen, N., et al. (2016) · Nature Communications · doi:10.1038/ncomms12350 · Cited by 48 · see citing works
Self-citation
- Authors
- Stefansson, H., Geirsson, R. T., Steinthorsdottir, V., Jonsson, H., Manolescu, A., Kong, A., Ingadottir, G., Gulcher, J., & Stefansson, K.
- Affiliations
- National University Hospital of Iceland (IS)
- deCODE Genetics (Iceland) (IS)
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-03-01
- Volume
- 17
- Issue
- 3
- Pages
- 555-559
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2098736824
- Cited by
- 228
- References
- 21
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 15 · 2019: 11 · 2018: 7 · 2017: 10 · 2016: 14 · 2015: 6 · 2014: 13 · 2013: 14 · 2012: 10
- FWCI
- 8.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Plant and fungal interactions
- Keywords
- endometriosis, familial aggregation, genetic susceptibility, kinship coefficient, founder effect, genealogical databases, Iceland, sisters, cousins, maternal and paternal inheritance, population-based study
- MeSH terms
- Endometriosis, Female, Genealogy and Heraldry, Humans, Iceland, Pedigree, Reference Values, Risk Factors, Cluster Analysis, Odds Ratio, Databases, Factual, Genetic Predisposition to Disease
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