Zondervan group

Research Overview

The Zondervan 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.  Of particular interest is the role epidemiological design principles can play in genetic association studies, and how in turn genetic/molecular findings can inform environmental epidemiological studies. 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. At WTCHG, we form part of the Genetic and Genomic Epidemiology Unit, co-led by Andrew Morris, Cecilia Lindgren, and Krina Zondervan.

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 ablation 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.

Our studies, and those of others, have shown that 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 the heritability is estimated around 52%. Relative recurrence risk (the risk of endometriosis in a female relative of a woman with endometriosis, compared to the general population) is difficult to calculate as the population prevalence is unknown. Estimates for siblings (ls) vary from 2.3 for self-reported endometriosis to 15 in sisters of women with more severe disease, based upon imaging studies. To date, it is unclear which genetic variants underlie susceptibility to the condition. The role of specific environmental factors also remains largely unknown.

Recent Publications

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. 2011. Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nature Genetics, 43, 51-4

Nica AC, Parts L, Glass D, Nisbet J, Barrett A, Sekowska M, Travers M, Potter S, Grundberg E, Small K, Hedman AK, Bataille V, Tzenova BJ, Surdulescu G, Dimas AS, Ingle C, Nestle FO, di Meglio P, Min JL, Wilk A, Hammond CJ, Hassanali N, Yang TP, Montgomery SB, O'Rahilly S, Lindgren CM, Zondervan KT, Soranzo N, Barroso I, Durbin R, Ahmadi K, Deloukas P, McCarthy MI, Dermitzakis ET, Spector TD. 2011. The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study. PLoS Genetics, e1002003

Anderson CA, Pettersson FH, Clarke GM, Cardon LR, Morris AP, Zondervan KT. 2010. Data quality control in genetic case-control association studies. Nature Protocols, 5, 1564-73.

Rogers PA, D'Hooghe TM, Fazleabas A, Gargett CE, Giudice LC, Montgomery GW, Rombauts L, Salamonsen LA, Zondervan KT. 2009. Priorities for endometriosis research: recommendations from an international consensus workshop. Reproductive Sciences, 16, 335-46.

Montgomery GW, Nyholt Dr, Zhao ZZ, Treloar SA, Painter JN, Missmer SA, Kennedy SH, Zondervan KT. 2008. The search for genes contributing to endometriosis risk. Human Reproduction Update, 14, 447-57.

Funding Sources

The Wellcome Trust; National Institutes of Health, US; World Endometriosis Research Fund; EU Public Health Programme

Research Area

Genomic epidemiology

Keywords

Genetic, genomic, environmental epidemiology; women's health; endometriosis; pelvic pain; infertility; study design