A Systematic Two-Sample Mendelian Randomization Analysis Identifies Shared Genetic Origin of Endometriosis and Associated Phenotypes
Aiara Garitazelaia,
Aintzane Rueda-Martínez,
Rebeca Arauzo,
Jokin de Miguel,
Ariadna Cilleros-Portet,
Sergi Marí,
Jose Ramon Bilbao,
Nora Fernandez-Jimenez,
Iraia García-Santisteban
Affiliations
Aiara Garitazelaia
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Aintzane Rueda-Martínez
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Rebeca Arauzo
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Jokin de Miguel
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Ariadna Cilleros-Portet
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Sergi Marí
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Jose Ramon Bilbao
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Nora Fernandez-Jimenez
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Iraia García-Santisteban
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain
Endometriosis, one of the most common gynecological disorders, is a complex disease characterized by the growth of endometrial-like tissue in extra-uterine locations and is a cause of pelvic pain and infertility. Evidence from observational studies indicate that endometriosis usually appears together with several other phenotypes. These include a list of autoimmune diseases, most of them more prevalent in women, anthropometric traits associated with leanness in the adulthood, as well as female reproductive traits, including altered hormone levels and those associated with a prolonged exposure to menstruation. However, the biological mechanisms underlying their co-morbidity remains unknown. To explore whether those phenotypes and endometriosis share a common genetic origin, we performed a systematic Two-Sample Mendelian Randomization (2SMR) analysis using public GWAS data. Our results suggest potential common genetic roots between endometriosis and female anthropometric and reproductive traits. Particularly, our data suggests that reduced weight and BMI might be mediating the genetic susceptibility to suffer endometriosis. Furthermore, data on female reproductive traits strongly suggest that genetic variants that predispose to a more frequent exposure to menstruation, through earlier age at menarche and shorter menstrual cycles, might also increase the risk to suffer from endometriosis.
