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Pott J, Horn K, Zeidler R, et al. Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian Randomization Study. Metabolites. 2021;11(11)doi: 10.3390/metabo11110738.
Pott, J., Horn, K., Zeidler, R., Kirsten, H., Ahnert, P., Kratzsch, J., Loeffler, M., Isermann, B., Ceglarek, U., & Scholz, M. (2021). Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian Randomization Study. Metabolites, 11(11), . https://doi.org/10.3390/metabo11110738
Pott, Janne, et al. "Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian Randomization Study." Metabolites vol. 11,11 (2021). doi: https://doi.org/10.3390/metabo11110738
Pott J, Horn K, Zeidler R, Kirsten H, Ahnert P, Kratzsch J, Loeffler M, Isermann B, Ceglarek U, Scholz M. Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian Randomization Study. Metabolites. 2021 Oct 28;11(11). doi: 10.3390/metabo11110738. PMID: 34822396; PMCID: PMC8624973.
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Metabolites. 2021 Oct 28;11(11). doi: 10.3390/metabo11110738.

Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian Randomization Study.

Metabolites

Janne Pott, Katrin Horn, Robert Zeidler, Holger Kirsten, Peter Ahnert, Jürgen Kratzsch, Markus Loeffler, Berend Isermann, Uta Ceglarek, Markus Scholz

Affiliations

  1. Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany.
  2. LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
  3. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany.

PMID: 34822396 PMCID: PMC8624973 DOI: 10.3390/metabo11110738

Abstract

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.

Keywords: Mendelian randomization; coronary artery disease; genome-wide association analysis; obesity; sexual dimorphism; steroid hormones

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