title: Genetic burden associated with varying degrees of disease severity in endometriosis.
abstract: Endometriosis is primarily characterized by the presence of tissue resembling endometrium outside the uterine cavity and is usually diagnosed by laparoscopy. The most commonly used classification of disease, the revised American Fertility Society (rAFS) system to grade endometriosis into different stages based on disease severity (I to IV), has been questioned as it does not correlate well with underlying symptoms, posing issues in diagnosis and choice of treatment. Using two independent European genome-wide association (GWA) datasets and top-level classification of the endometriosis cases based on rAFS [minimal or mild (Stage A) and moderate-to-severe (Stage B) disease], we previously showed that Stage B endometriosis has greater contribution of common genetic variation to its aetiology than Stage A disease. Herein, we extend our previous analysis to four endometriosis stages [minimal (Stage I), mild (Stage II), moderate (Stage III) and severe (Stage IV) disease] based on the rAFS classification system and compared the genetic burden across stages. Our results indicate that genetic burden increases from minimal to severe endometriosis. For the minimal disease, genetic factors may contribute to a lesser extent than other disease categories. Mild and moderate endometriosis appeared genetically similar, making it difficult to tease them apart. Consistent with our previous reports, moderate and severe endometriosis showed greater genetic burden than minimal or mild disease. Overall, our results provide new insights into the genetic architecture of endometriosis and further investigation in larger samples may help to understand better the aetiology of varying degrees of endometriosis, enabling improved diagnostic and treatment modalities.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia yadav.sapkota@qimrberghofer.edu.au.
authors.forename: Yadav
authors.initials: Y
authors.lastname: Sapkota
authors.affiliation: Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia Public Health Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gordon
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.affiliation: Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia Public Health Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.affiliation: Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Rahmioglu
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: MacGregor
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia Public Health Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: McEvoy
authors.affiliation: Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: Public Health Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia Division of Genetics, Hunter Area Pathology Service, Newcastle, New South Wales, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Krina T
authors.initials: KT
authors.lastname: Zondervan
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
mesh_terms: D004715:Endometriosis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D012720:Severity of Illness Index
keywords: endometriosis; genetic burden; genome-wide association studies; polygenic prediction; rAFS classification system