{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:39Z","timestamp":1787028579126,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometriosis has a significant impact on the social, psychological, psychosomatic, and physical aspects of women\u2019s lives. There is increasing evidence that endometriosis has to be seen as a systemic and complex disorder with a multifactorial etiology, accompanied by numerous other pathologies, such as mental disorders and even cancer. Herein, we analyzed Disability-Adjusted Life Years (DALYs) and Years Lived with Disability (YLDs) generated from the Global Burden of Disease Study (GBD 2021), which are key metrics used to measure the worldwide impact of diseases. Besides, differential gene expression data generated from the Turku Endomet Database were calculated. Briefly, log2-transformed gene expression counts were investigated using linear modeling with the function expression ~ condition to generate log2 fold changes and p-values for each gene. This enabled a precise comparative analysis of mRNA expression levels between control endometrium and various endometriosis-affected tissues, including ovarian endometrioma, peritoneal lesions, and deep endometriosis. Expression patterns of specific genes related to pain and malignant turnover within endometriosis samples and controls have been analyzed. The identification of upregulated genes like FOS, DES, SIRT1, SBDS, SRF, SPN, P2RX1, TEAD3, and SLITRK3, alongside downregulated genes such as KIF22, KIF25, GAS2L2, and HINT3, highlights a broad transcriptional reprogramming within endometriotic tissues. The clustering analysis, which reveals pain-related genes (SRP14\/BMF, GDAP1, MLLT10, BSN, and NGF), further solidifies the genetic basis for the chronic and often debilitating pain experienced by patients with endometriosis. In 2021, women with endometriosis experienced the highest rates of total YLDs at 19.98%, with anxiety contributing 17.21% and major depression 8.12%, equating to mean YLDs of 15\u201324 years. In conclusion, our findings reinforce the need for adopting a holistic, psychosomatic approach to managing endometriosis. The identified genetic markers related to pain provide a biological basis for the profound physical suffering. At the same time, the robust DALYs and YLDs data quantify the devastating impact on mental health, particularly highlighting the significant burden of depression and anxiety.<\/jats:p>","DOI":"10.3390\/ijms27010151","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:57:18Z","timestamp":1766487438000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endometriosis: From Genes to Global Burden"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3344-5060","authenticated-orcid":false,"given":"Pawel","family":"Kordowitzki","sequence":"first","affiliation":[{"name":"Department of Basic and Preclinical Sciences, Nicolaus Copernicus University, 87-100 Torun, Poland"},{"name":"Department of Gynaecology, European Competence Centre for Ovarian Cancer, Charit\u00e9 Medical University, Augustenburgerplatz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam P.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics, Faculty of Computing and Data Sciences, Boston University, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Mechsner","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, European Competence Centre for Ovarian Cancer, Charit\u00e9 Medical University, Augustenburgerplatz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. 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