Our group focuses on the integration of genetic, molecular, and environmental epidemiological research methods in uncovering the aetiology of endometriosis, and related women's health conditions that carry a substantial public health burden. We are based both at the Wellcome Trust Centre for Human Genetics (WTCHG) and the Nuffield Dept of Obstetrics & Gynaecology (NDOG) in Oxford, and collaborate with a network of other research groups (inter)nationally.
Endometriosis is a common condition, affecting millions of women worldwide, for which the causes remain unknown. It is characterised by the presence of endometrial-like tissue in sites outside the uterus, causing pelvic pain and subfertility. The need for surgery to confirm diagnosis means exact population prevalence rates are unknown, but estimates vary between 3-10% of women in their reproductive years. Endometriosis has a major impact on health-related quality of life and work productivity, with treatment options limited to hormonal drugs to suppress ovarian function, surgical removal of endometriotic lesions and, if necessary, removal of the pelvic organs. In 2002, the annual direct and indirect economic costs of endometriosis in the US alone were estimated between $2.3 and $22 billion, 3 to 25 times higher than - for example - Crohn's disease, and similar to migraine.
Endometriosis is a complex disorder, caused by the interplay between genetic and environmental factors. Familial aggregation of endometriosis has been shown both in humans and nonhuman primates, and heritability is estimated around 52%. We have led the largest, collaborative, genome-wide association studies of endometriosis to date, involving >4,000 women with endometriosis and > 10,000 controls in the International Endogene Consortium. To date, our work has resulted in the identification of 7 of the now 9 known genetic loci involved in the aetiology of endometriosis. These results have provided the first robust insights into potential pathways of disease pathogenesis. We are exploring how they can aid biomarker discovery, and the identification of novel drug targets.
In our prospective study ENDOX at the Endometriosis CaRe centre in Oxford, we recruit all women undergoing a laparoscopy for symptoms suggestive of endometriosis or for tubal sterilisation, collecting biological samples and detailed surgical and clinical information. The samples and data collected will allow us to investigate the functionality of the identified genetic loci, and understand the molecular epidemiological basis for disease sub-types, using genomic, transcriptomic and epigenomic studies.
We strongly believe that future studies will continue to require collaborations with other research centres collecting biological samples from women with and without endometriosis. Together with the Boston Centre for Endometriosis at Harvard University, we are leading a large-scale initiative - EPHect - aimed at global standardisation and harmonisation of data and sample collection protocols in endometriosis research: endometriosisfoundation.org/ephect. This initiative currently includes >30 academic and industrial collaborators, and provides a new platform for large-scale collaborative work in the field of endometriosis.
For a full list: Publications
Rahmioglu N, Nyholt DR, Morris AP, Missmer SA, Montgomery GW, Zondervan KT. Genetic variants underlying endometriosis risk: insights from eight genome-wide association and replication datasets in 11,000 cases and 32,000 controls. Hum Reprod Update, 2014 in press.
Nyholt DR, Low SK, Anderson CA, Painter JN, Uno S, Morris AP, MacGregor S, Gordon SD, Henders AK, Martin NG, Attia J, Holliday EG, McEvoy M, Scott RJ, Kennedy SH, Treloar SA, Missmer SA, Adachi S, Tanaka K, Nakamura Y, [Zondervan KT, Zembutsu H, Montgomery GW]. Genome-wide association meta-analysis identifies new endometriosis risk loci. Nature Genetics 2012;44:1355-9
Painter JN, Anderson CA, Nyholt DR, Macgregor S, Lin J, Lee SH, Lambert A, Zhao Z, Roseman F, Guo Q, Gordon SD, Wallace L, Henders AK, Visscher PM, Kraft P, Martin NG, Morris AP, [Treloar SA, Kennedy SH, Missmer SA, Montgomery GW, Zondervan KT]. Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nature Genetics 2011;43:51-4
Grundberg E, Small KS, Hedman AK, Nica AC, Buil A, Keildson S, Bell JT, Yang T-P, Barrett A, Nisbet J, Sekowska M, Wilk A, Shin S-Y, Glass D, Travers M, Min JL, Ring S, Ho K, Thorleifsson G, Kong A, Thorsteindottir U, Ainali BC, Dimas AS, Hassanali N, Ingle C, Knowles D, Krestyaninova M, Lowe CE, Meduri E, Di Meglio P, Montgomery SB, Parts L, Potter S, Surdulescu G, Tsaprouni L, Tsoka S, Bataille V, Durbin R, Nestle FO, O’Rahilly S, Soranzo N, Lindgren SM, Zondervan KT, Ahmadi K, Schadt EE, Stefansson K, Davey Smith G, McCarthy MI, Deloukas P, Dermitzakis ET, Spector TD, for the MuTHER consortium. Mapping cis and trans regulatory effects across multiple tissues in twins: the MuTHER Study. Nature Genetics 2012;44:1084-1089.Min JL, Nicholson G, Halgrimsdottir I, Almstrup K, Petri A, Barrett A, Travers M, Rayner NW, Mägi R, Pettersson FH, Broxholme J, Neville MJ, Wills QF, Cheeseman J; The GIANT Consortium; The MolPAGE Consortium, Allen M, Holmes CC, Spector TD, Fleckner J, McCarthy MI, Karpe F, Lindgren CM, Zondervan KT. Coexpression Network Analysis in Abdominal and Gluteal Adipose Tissue Reveals Regulatory Genetic Loci for Metabolic Syndrome and Related Phenotypes. PLoS Genetics 2012;8:e1002505
Nnoaham KE, Hummelshoj L, Webster P, d'Hooghe T, de Cicco Nardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH, Zondervan KT; World Endometriosis Research Foundation Global Study of Women's Health consortium. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertility & Sterility 2011;96:366-373.
The Wellcome Trust; National Institutes of Health, US; World Endometriosis Research Fund; EU Public Health Programme