{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:00:17Z","timestamp":1785438017798,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1301103"],"award-info":[{"award-number":["2021YFA1301103"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2505200"],"award-info":[{"award-number":["2022YFC2505200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2505203"],"award-info":[{"award-number":["2022YFC2505203"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32500519"],"award-info":[{"award-number":["32500519"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32570728"],"award-info":[{"award-number":["32570728"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study examined sex\u2010stratified effects of R\u2010spondin 3 (RSPO3) expression levels on body fat and blood lipids and their potential mediation effects through sex hormones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a sex\u2010stratified genome\u2010wide association study (GWAS) of RSPO3 protein (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200918,529 men and 21,323 women). We used two\u2010sample Mendelian randomization (MR) to examine associations of RSPO3 expression with the outcomes. Sex\u2010stratified MR estimates were compared using the pairwise\n                      <jats:italic>z<\/jats:italic>\n                      score test and Cochran's\n                      <jats:italic>Q<\/jats:italic>\n                      test. We conducted two\u2010step MR analyses to explore mediation effects through sex hormones.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sex\u2010stratified GWAS identified nine loci associated with RSPO3 protein levels, including three novel signals and four female\u2010stratified loci. In women, RSPO3 protein levels were associated with visceral adipose tissue (\u03b2\u2009=\u20090.22, 95% CI\u2009=\u20090.10 to 0.34), waist circumference (0.10, 0.05 to 0.15), hip circumference (0.10, 0.05 to 0.15), triglycerides (0.22, 0.18 to 0.26), high\u2010density lipoprotein cholesterol (\u22120.17, \u22120.21 to \u22120.13), and apolipoprotein A (\u22120.11, \u22120.15 to \u22120.06). We also observed sex differences in these associations. Two\u2010step MR showed that RSPO3 protein levels affected six outcomes via sex hormone\u2010binding globulin in women, with little evidence in men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings indicated that\n                      <jats:italic>RSPO3<\/jats:italic>\n                      could be a drug target for regulating body fat distribution and blood lipids in women.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/oby.70252","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:18:21Z","timestamp":1783567101000},"page":"1623-1634","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Sex\u2010Stratified Effects of\n                    <scp>RSPO3<\/scp>\n                    Expression on Body Fat and Blood Lipids: An Omics Mendelian Randomization Study"],"prefix":"10.1002","volume":"34","author":[{"given":"Yihua","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanhui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"MRC Integrative Epidemiology Unit at University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9383-7656","authenticated-orcid":false,"given":"Jiqiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Shanghai Digital Medicine Innovation Center, Lifecycle Health Management Center, Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"MRC Integrative Epidemiology Unit at University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.02.010"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202207152"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-02-0187"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16592-z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113261"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201062695\u20108"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61126-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0455"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.101141"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0682-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06592-6"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3406"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02335-7"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba3066"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/2020.08.10.244293"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30931-2"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215597579"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.13732"},{"key":"e_1_2_11_23_1","article-title":"Proteome\u2010Wide Association Studies for Blood Lipids and Comparison With Transcriptome\u2010Wide Association Studies","volume":"6","author":"Zhang D.","year":"2025","journal-title":"HGG Advances"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0222362"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101382"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00757-1"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-021-00092-5"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx034"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59034-4"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae210"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/db24-0762"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042018817750823"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.01.012"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315246"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63410-5"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax9605"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/2042-6410-3-13"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3214-z"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes9010020"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1106083108"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.01.009"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702305104"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1136370"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-16-0070"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.06.033"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2023.2165908"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(99)90146-4"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15704-y"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3034"}],"container-title":["Obesity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/oby.70252","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/oby.70252","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/oby.70252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:30:07Z","timestamp":1785436207000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/oby.70252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/oby.70252"],"URL":"https:\/\/doi.org\/10.1002\/oby.70252","archive":["Portico"],"relation":{},"ISSN":["1930-7381","1930-739X"],"issn-type":[{"value":"1930-7381","type":"print"},{"value":"1930-739X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"assertion":[{"value":"2025-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}