Academic Journal
Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study
| Τίτλος: | Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study |
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| Συγγραφείς: | Pott, Janne, Horn, Katrin, Zeidler, Robert, Kirsten, Holger, Ahnert, Peter, Kratzsch, Jürgen, Loeffler, Markus, Isermann, Berend, Ceglarek, Uta, Scholz, Markus |
| Publication Status: | publishedVersion |
| Στοιχεία εκδότη: | MDPI, 2021. |
| Έτος έκδοσης: | 2021 |
| Συλλογή: | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Original Material: | urn:nbn:de:bsz:15-qucosa2-852802 |
| Θεματικοί όροι: | steroid hormones, sexual dimorphism, genome-wide association analysis, Mendelian randomization, coronary artery disease, obesity, info:eu-repo/classification/ddc/540, ddc:540 |
| Περιγραφή: | 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. |
| Original Identifier: | oai:qucosa:de:qucosa:85280 |
| Τύπος εγγράφου: | Article Text |
| Γλώσσα: | English |
| ISSN: | 2218-1989 |
| Relation: | 738 |
| Διαθεσιμότητα: | https://ul.qucosa.de/id/qucosa%3A85280 https://ul.qucosa.de/api/qucosa%3A85280/attachment/ATT-0/ |
| Rights: | info:eu-repo/semantics/openAccess |
| Αριθμός Καταχώρησης: | edsndl.DRESDEN.oai.qucosa.de.qucosa.85280 |
| Βάση Δεδομένων: | Networked Digital Library of Theses & Dissertations |
| ISSN: | 22181989 |
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