News · May 29, 2025

David Healy Award 2025 presented to Lindsay Guare

The David Healy Award for best Oral Presentation by an Early Career Scientist was presented to Lindsay Guare at the closing ceremony of the 16th World Congress on Endometriosis for her work on Expanding the Genetic Landscape of Endometriosis: Integrating Multi-omics with a Genome-wide Meta-analysis of Over 900,000 Genetically Diverse Women

L Guare1, J Das1, A Rajagopalan1, L Caruth1, S Namba2, Y Okada2, Y Shirai3, Y Yamamoto3, A Akerele4, J Jaworski4, D Velez-Edwards4, A Hill5, J Shortt5, N Elhadad6, G Jarvik7, L Kottyan8, Y Luo9, W Wei10, C Weng6, S Chapman11, Y Shi11, W Zhou11, A Mulford12, A Sanders12, B Brumpton13, E Moreno13, T Chen15, V Rovite14, Y Lin15,S Setia- Verma1

1University Of Pennsylvania, Philadelphia, United States
2The University of Tokyo, Japan
3Osaka University, Suita, Japan
4Vanderbilt University Medical Center, Nashville, United States
5Colorado Center for Precision Medicine, Aurora, United States
6Columbia University, New York City, United States
7University of Washington, Seattle, United States
8Cincinnati Children’s Hospital Medical Center, Cincinnati, United States
9Northwestern University, Evanston, United States
10Vanderbilt University, Nashville, United States
11The Broad Institute, Cambridge, United States
12Endeavor Health, Evanston, United States
13Norwegian University of Science and Technology, Trondheim, Norway
14Latvian Biomedical Research and Study Centre, Latvia
15National Health Research Institutes, Maoli County, Taiwan

Country: United States of America Introduction/Background

Endometriosis is a complex heritable disorder requiring comprehensive genomic investigation

across diverse populations. Previous studies have been somewhat limited by European-centric data. The Global Biobank Meta-Analysis Initiative (GBMI) enables large-scale genomic analysis across multiple genetic ancestry groups, complemented by computational multi-omic and single cell analyses to understand disease mechanisms.

Materials and Methods

We performed a Genome-Wide Association Study (GWAS) meta-analysis across 14 biobanks worldwide, with 31% non-European samples. Multiple endometriosis phenotype definitions were analyzed, including broad and surgically-confirmed cases. Post-GWAS analyses included ancestry-stratified heritability estimation and fine-mapping. We conducted Transcriptome- wide and Proteome-wide association analyses, followed by single-cell analyses of implicated genes. Integration of multi-omic data through Mergeomics analysis enabled comprehensive pathway enrichment assessment.

Results

The GWAS (N=928,413 : 44,125 cases) identified 45 significant loci using a broad phenotype definition, including seven previously-unreported signals and the first genome-wide significant locus (POLR2M) in African ancestry. Narrow phenotypes and surgically confirmed cases replicated known loci near CDC42 and SYNE1. Observed heritability was consistent (10-12%) across ancestral groups. Cross-ancestry fine-mapping revealed putative causal variants in 38 loci. Multi-omic imputed association analyses identified 11 significantly-associated gene transcripts (two previously unknown: DTD1 and CCDC88B), two intronic splicing events (within PGR and NSRP1), and one protein, RSPO3. In silico single-cell analyses prioritized 18 disease-relevant cell types including venous cells and macrophages. The results of these analyses specified key players in enriched molecular pathways involving immunopathogenesis, angiogenesis, Wnt signaling, and balance between proliferation, differentiation, and migration of endometrial cells as major hallmarks in genomics of endometriosis.

Conclusion

This diverse GWAS combined with transcriptomic, splice-omic, proteomic, and single-cell analyses revealed novel genetic associations and molecular mechanisms in endometriosis. The identification of ancestry-specific variants and pathway interactions provides multiple targets for developing precise therapeutic interventions across diverse populations.

Key words: Genome wide association analyses, multi-omic data integration, diverse populations

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News ·

Rodolphe Maheux Award 2025 presented to Amelia Mardon

The 2025 Rodolphe Maheux Award for best Oral Presentation by an Early Career Clinician was awarded to Amelia Mardon at the closing ceremony of the 16th World Congress on Endometriosis for her presentation on Pain Science Education Concepts for Pelvic Pain: An e-Delphi of Expert Clinicians

A Mardon1,2, H Leake1, M Wilson2,3, E Karran2, R Parker4, R Malani5, L Moseley2, J Chalmers2

1NICM Health Research Institute, Western Sydney University, Westmead, Australia
2IIMPACT in Health, UniSA, Adelaide, Australia
3Persistent Pain Research Group, UniSA, Adelaide, Australia
4Department of Anaesthesia and Perioperative Medicine, University of Cape Town, Cape Town, South Africa
5MGM School of Physiotherapy, Aurangabad, A constituent unit of MGMIHS, Maharashtra, India

Country: Australia

Introduction/Background

Pain science education (PSE) involves learning about the biology of pain. However, PSE is yet to be thoroughly investigated for persistent pelvic pain potentially due to the lack of targeted curricula. This study gained consensus on PSE learning concepts important for persistent pelvic pain according to expert clinicians.

Materials and Methods

A three-round e-Delphi survey was conducted to generate and gain consensus on important PSE learning concepts for female persistent pelvic pain among 20 international, multidisciplinary expert clinicians. Learning concepts generated by clinicians were rated by importance using a six-point Likert scale. Concepts were considered important if they had a median rating important >3.0. Consensus on importance rating was considered reached for items with an interquartile range <1.0.

Results

The panel included expert clinicians from seven countries and six healthcare professions. Most clinicians (40%) had 20+ years of experience in pelvic pain. Overall, the expert clinicians generated 125 PSE learning concepts that were considered important for persistent pelvic pain; 92 (73.6%) learning concepts reached consensus on their importance rating. Of the 125 learning concepts, 102 were generated for persistent pelvic pain in general, and were categorised into 13 overarching PSE concepts (e.g., persistent pelvic pain involves changes to the brain and nervous system; many factors influence persistent pelvic pain). Sixteen concepts were generated for specific pelvic pain conditions (e.g., endometriosis) and seven concepts for specific life stages (e.g., adolescence).

Conclusion

This study provides the first list of key PSE concepts for persistent pelvic pain developed by expert clinicians. These concepts share similarities to those valued by consumers.1 Taken together, they provide a framework for developing and implementing PSE curricula for persistent pelvic pain in research and clinical settings.

Key words

Pain science education, pelvic pain, patient education

References

  1. Mardon AK, Chalmers KJ, Heathcote LC, Curtis LA, Freedman L, Malani R, Parker R, Neumann PB, Moseley GL, Leake HB. “I wish I knew then what I know now”—pain science education concepts important for female persistent pelvic pain: a reflexive thematic analysis. Pain. 2024 Sep 1;165(9):1990-2001.

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News · November 30, 2023

David Healy Award 2023 presented to Marcela Haro

The David Healy Award for best Scientific Abstract was presented to Marcela Haro at the closing ceremony of the 15th World Congress on Endometriosis for her work on how Heterogeneous Immune Responses Underlie Subtype-Specific and Patient-Specific Heterogeneity in Endometriosis.

Haro M1,2, Fonseca M1,2, Abbasi F1,2, Goodridge H3,4, Siedhoff M5, Jefferies C6, Truong M5, Wright K5, Anglesio M 7,8, Medeiros F9, Lawrenson K1,2,10,11, Yu P10,2
1Women’s Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, United States of America, 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center , Los Angeles, United States of America, 3Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, United States of America, 4Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, United States of America, 5Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, United States of America, 6 Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, United States of America, 7 Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada, 8British Columbia’s Gynecological Cancer Research (OVCARE) Program, University of British Columbia, Vancouver General Hospital, and BC Cancer, Vancouver, Canada, 9Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, United States of America, 10Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, United States of America, 11Center for Bioinformatics and Functional
Genomics, Cedars-Sinai Medical Center, Los Angeles, United States of America

Introduction:
Endometriosis is characterized by endometrial-type glands and stroma growing outside of the uterine cavity, evading the typical cell-intrinsic and cell-extrinsic safeguards (including immune surveillance) that should prevent cells from surviving at ectopic locations. Chronic inflammation and dysregulation in the immune response contribute to the pathogenesis of endometriosis, however, little is understood regarding how immune dysregulation contributes to the extensive heterogeneity that characterizes endometriosis.

Aim:
This research seeks to phenotype the immune repertoire in endometriosis and explore the dysregulation in the molecular signals in the tissue microenvironment that influences immune cell recruitment and function.

Materials and Methods:
Single cell RNA sequencing was applied to >370,000 cells from endometriosis, eutopic endometrium, unaffected ovary and endometriosis-free peritoneum. All specimens were subjected to pathology review and genotyping for somatic variants in commonly mutated genes.

Results:
Endometriosis patients could be stratified into ‘immune-hot’ or ‘immune-cold’ subgroups based on the presence of lymphoid aggregates and germinal centers proximal to lesions. B-cells and plasma cells were particularly enriched in endometriosis. Elevated autoreactive antibodies, B-cell survival and recruitments signals and an interferon signature are seen in endometriosis.

Conclusion and impact:
Extensive heterogeneity in immune responses to endometriosis may explain, at least in part, the heterogenous presentations and symptoms associated with disease. Ongoing experiments are exploring the therapeutic potential of the anti-CD20 monoclonal antibody for patients with elevated B-cell dysfunction. This research is providing clinically relevant insights into the role of B-cells in the pathogenesis of endometriosis and potential targets for both diagnosis and therapeutics.

 

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News ·

Rodolphe Maheux Award 2023 presented to Scott MacKenzie

The 2023 Rodolphe Maheux Award for best Clinical Abstract was presented to Scott MacKenzie at the closing ceremony of the 15th World Congress on Endometriosis for his work on how Genome-wide association reveals a locus in Neuregulin 3 associated with gabapentin efficacy in women with chronic pelvic pain.

MacKenzie S1, Rahmioglu N2,3, Collins F1, Coxon L3, Vincent K3, Zondervan K2,3, Horne A1, Whitaker L1
1MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom, 2Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 3Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United Kingdom

Introduction:
Chronic pelvic pain (CPP) in women with no obvious pelvic pathology has few evidence-based treatment options. Our recent multicentre randomised controlled trial (GaPP2) in women with CPP showed that gabapentin did not relieve pain and was associated with higher rates of side-effects than placebo. However, the data suggest that subgroups of women could benefit from gabapentin.

Aim:
To identify if common genetic variants are associated with gabapentin response in women with CPP with no obvious pelvic pathology.

Materials and Methods:
We conducted a genome-wide association study of gabapentin response, using participants from GaPP2. Two phenotypes were investigated: gabapentin analgesic response (≥30% reduction in worst and/or average pain), and side-effect burden (≥3 side-effects reported). Standard genetic quality control was conducted followed by imputation to HRC reference panel. Frequentist association analysis was conducted in SNPTEST including autosomes and chromosome X.

Results:
93 participants provided salivary samples for genotyping (82 passed quality control) and 5,522,729 SNPs were tested for association (n=29 ≥30% vs. n=42 <30% reduction in worst and/or average pain scores). One genome-wide significant association with gabapentin analgesic response was identified, rs4442490, an intron variant located in Neuregulin 3 (NRG3) at 10q23.1 (p=2.11×10−8; OR=18.82 (95%CI 4.86–72.83);
MAF=0.42). NRG3 is expressed predominantly in brain tissues and involved in nervous system maintenance/repair. No SNPs reached genome-wide significance for gabapentin side-effect burden.

Conclusion and impact:
A locus in NRG3 is associated with gabapentin efficacy in women with CPP with no obvious pelvic pathology, highlighting the possibility of a precision medicine approach to symptom management.

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