{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:16:08Z","timestamp":1761848168376,"version":"build-2065373602"},"reference-count":29,"publisher":"Walter de Gruyter GmbH","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0073_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Precocious puberty in girls is a condition marked by the early onset of secondary sexual characteristics, with vascular factors like uterine artery pulsatility index having been suggested as potential indicators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0073_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed Mendelian randomization (MR) analysis using genetic instruments from large-scale genome-wide association studies (GWAS) datasets, including ebi-a-GCST008403, ukb-a-250, and ukb-b-11971, to evaluate the relationship between arterial stiffness and precocious puberty. Exposure and outcome data were sourced from the GWAS Catalog, eQTLGen, and the R11_E4_PREPUB dataset. The TwoSampleMR package was employed to assess causal relationships, with several MR methods applied, including inverse variance weighted, MR Egger, weighted median, and mode-based methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0073_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis of arterial stiffness using ebi-a-GCST008403, ukb-a-250, and ukb-b-11971 datasets did not show a statistically significant causal relationship with precocious puberty. The IVW method showed an OR of 0.707 (p=0.885) for arterial stiffness, indicating no reliable association. The investigation into MMP2 also yielded non-significant results across all methods, with an OR of 0.778 (p=0.330) from the IVW method. However, the analysis of MMP9 revealed a significant association with precocious puberty, showing an OR of 3.89 (p=0.004) using the IVW method, and an OR of 3.96 (p=0.027) from the Weighted Median method, indicating a strong positive effect of MMP9 on precocious puberty\u00a0risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0073_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that while arterial stiffness and other MMPs do not have a significant causal role, MMP9 may significantly increase the risk of precocious puberty in\u00a0girls.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0073","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T17:59:52Z","timestamp":1758823192000},"page":"1195-1208","source":"Crossref","is-referenced-by-count":0,"title":["Causal analysis of uterine artery pulsatility index-related proteins and the risk of precocious puberty in girls: a Mendelian randomization study"],"prefix":"10.1515","volume":"38","author":[{"given":"Yi","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pediatrics , Huzhou Maternity & Child Health Care Hospital , Huzhou City , Zhejiang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengfeng","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Huzhou Maternity & Child Health Care Hospital , Huzhou City , Zhejiang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"2025103018011142697_j_jpem-2025-0073_ref_001","doi-asserted-by":"crossref","unstructured":"Paesano, PL, Colantoni, C, Mora, S, di Lascio, A, Ferrario, M, Esposito, A, et al.. Validation of an accurate and noninvasive tool to exclude female precocious puberty: pelvic ultrasound with uterine artery pulsatility index. AJR Am J Roentgenol 2019;213:451\u20137. https:\/\/doi.org\/10.2214\/AJR.18.19875.","DOI":"10.2214\/AJR.18.19875"},{"key":"2025103018011142697_j_jpem-2025-0073_ref_002","doi-asserted-by":"crossref","unstructured":"Battaglia, C, Regnani, G, Mancini, F, Iughetti, L, Venturoli, S, Flamigni, C. Pelvic sonography and uterine artery color Doppler analysis in the diagnosis of female precocious puberty. Ultrasound Obstet Gynecol 2002;19:386\u201391. https:\/\/doi.org\/10.1046\/j.1469-0705.2002.00669.x.","DOI":"10.1046\/j.1469-0705.2002.00669.x"},{"key":"2025103018011142697_j_jpem-2025-0073_ref_003","doi-asserted-by":"crossref","unstructured":"Battaglia, C, Regnani, G, Mancini, F, Iughetti, L, Bernasconi, S, Volpe, A, et al.. Isolated premature pubarche: ultrasonographic and color Doppler analysis--a longitudinal study. J\u00a0Clin Endocrinol Metab 2002;87:3148\u201354. https:\/\/doi.org\/10.1210\/jcem.87.7.8632.","DOI":"10.1210\/jcem.87.7.8632"},{"key":"2025103018011142697_j_jpem-2025-0073_ref_004","unstructured":"Li, H, Ding, L, Ding, J, et al.. The influence of CD40\/CD40L, MMP2\/MMP9 on uterine artery blood flow and their expression in recurrent miscarriage. Altern Ther Health Med 2024:AT10174."},{"key":"2025103018011142697_j_jpem-2025-0073_ref_005","doi-asserted-by":"crossref","unstructured":"Fung, K, Ram\u00edrez, J, Warren, HR, Aung, N, Lee, AM, Tzanis, E, et al.. Genome-wide association study identifies loci for arterial stiffness index in 127,121 UK Biobank participants. Sci Rep 2019;9:9143. https:\/\/doi.org\/10.1038\/s41598-019-45703-0.","DOI":"10.1038\/s41598-019-45703-0"},{"key":"2025103018011142697_j_jpem-2025-0073_ref_006","doi-asserted-by":"crossref","unstructured":"Magno, R, Maia, AT. gwasrapidd: an R package to query, download and wrangle GWAS catalog data. Bioinformatics 2020;36:649\u201350. https:\/\/doi.org\/10.1093\/bioinformatics\/btz605.","DOI":"10.1093\/bioinformatics\/btz605"},{"key":"2025103018011142697_j_jpem-2025-0073_ref_007","doi-asserted-by":"crossref","unstructured":"V\u00f5sa, U, Claringbould, A, Westra, HJ, Bonder, MJ, Deelen, P, Zeng, B, et al.. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet 2021;53:1300\u201310. https:\/\/doi.org\/10.1038\/s41588-021-00913-z.","DOI":"10.1038\/s41588-021-00913-z"},{"key":"2025103018011142697_j_jpem-2025-0073_ref_008","doi-asserted-by":"crossref","unstructured":"Zhu, Z, Zhang, F, Hu, H, Bakshi, A, Robinson, MR, Powell, JE, et al.. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. 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