{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:01:04Z","timestamp":1777654864669,"version":"3.51.4"},"reference-count":74,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["713-24120"],"award-info":[{"award-number":["713-24120"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014913","name":"Freistaat Sachsen","doi-asserted-by":"publisher","award":["14505\/2470"],"award-info":[{"award-number":["14505\/2470"]}],"id":[{"id":"10.13039\/501100014913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013295","name":"Helmholtz Zentrum M\u00fcnchen","doi-asserted-by":"publisher","award":["HIMAG-108"],"award-info":[{"award-number":["HIMAG-108"]}],"id":[{"id":"10.13039\/501100013295","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ZX1906B"],"award-info":[{"award-number":["01ZX1906B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Steroid hormones act as important regulators of physiological processes including gene expression. They provide possible mechanistic explanations of observed sex-dimorphisms in obesity and coronary artery disease (CAD). Here, we aim to unravel causal relationships between steroid hormones, obesity, and CAD in a sex-specific manner. In genome-wide meta-analyses of four steroid hormone levels and one hormone ratio, we identified 17 genome-wide significant loci of which 11 were novel. Among loci, seven were female-specific, four male-specific, and one was sex-related (stronger effects in females). As one of the loci was the human leukocyte antigen (HLA) region, we analyzed HLA allele counts and found four HLA subtypes linked to 17-OH-progesterone (17-OHP), including HLA-B*14*02. Using Mendelian randomization approaches with four additional hormones as exposure, we detected causal effects of dehydroepiandrosterone sulfate (DHEA-S) and 17-OHP on body mass index (BMI) and waist-to-hip ratio (WHR). The DHEA-S effect was stronger in males. Additionally, we observed the causal effects of testosterone, estradiol, and their ratio on WHR. By mediation analysis, we found a direct sex-unspecific effect of 17-OHP on CAD while the other four hormone effects on CAD were mediated by BMI or WHR. In conclusion, we identified the sex-specific causal networks of steroid hormones, obesity-related traits, and CAD.<\/jats:p>","DOI":"10.3390\/metabo11110738","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T23:51:36Z","timestamp":1635465096000},"page":"738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Sex-Specific Causal Relations between Steroid Hormones and Obesity\u2014A Mendelian Randomization Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5983-5331","authenticated-orcid":false,"given":"Janne","family":"Pott","sequence":"first","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany"},{"name":"LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5307-6936","authenticated-orcid":false,"given":"Katrin","family":"Horn","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany"},{"name":"LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zeidler","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-7950","authenticated-orcid":false,"given":"Holger","family":"Kirsten","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany"},{"name":"LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-0856","authenticated-orcid":false,"given":"Peter","family":"Ahnert","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany"},{"name":"LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Kratzsch","sequence":"additional","affiliation":[{"name":"LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"},{"name":"Institute of Laboratory Medicine, Clinical Chemistry 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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uta","family":"Ceglarek","sequence":"additional","affiliation":[{"name":"LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany"},{"name":"Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Scholz","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany"},{"name":"LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, 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