{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:08:16Z","timestamp":1784549296503,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder with complex pathogenesis and limited targeted therapeutic options. This study presents a proteomics\u2010informed approach to identify potential plasma protein targets for PCOS intervention using causal inference methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a comprehensive proteome\u2010wide Mendelian randomization analysis by integrating 1\u2009Mb plasma cis\u2010acting protein quantitative trait loci datasets with PCOS genome\u2010wide association study summary statistics. To enhance robustness, we applied complementary approaches including summary\u2010data\u2010based MR, the Heterogeneity in Dependent Instruments test, and colocalization analysis. Identified targets were further assessed for druggability using curated drug databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The MR analysis revealed 33 plasma proteins significantly associated with PCOS risk. Among these, FGF23 and SH2B3 showed the strongest evidence of a causal role, supported by SMR, HEIDI, and colocalization analyses. FGF23 was positively associated with PCOS risk and implicated in inflammatory and metabolic pathways, while SH2B3 was inversely associated and linked to anti\u2010inflammatory signalling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study establishes a causal link between specific plasma proteins and PCOS and identifies FGF23 and SH2B3 as promising candidates for targeted drug development. These findings demonstrate the value of proteomics\u2010integrated genetic analyses in uncovering novel therapeutic avenues for complex diseases like PCOS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.71285","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T03:33:48Z","timestamp":1758598428000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Effects of Plasma Proteins in Polycystic Ovary Syndrome: A Proteome\u2010Wide Mendelian Randomization Study"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3526-4194","authenticated-orcid":false,"given":"Tong","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Gynecology Guangan Hospital of Traditional Chinese Medicine Guangan Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4841-7038","authenticated-orcid":false,"given":"Pengfei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.231251"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1358755"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084110"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.02.078"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0175-2"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100195"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.01.028"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008517"},{"key":"e_1_2_14_10_1","doi-asserted-by":"crossref","unstructured":"PLoS Genet.14 no.12(2018):e1007813. 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