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

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,...

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Autores principales:	Janne Pott, Katrin Horn, Robert Zeidler, Holger Kirsten, Peter Ahnert, Jürgen Kratzsch, Markus Loeffler, Berend Isermann, Uta Ceglarek, Markus Scholz
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	steroid hormones sexual dimorphism genome-wide association analysis Mendelian randomization coronary artery disease obesity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/83f02438365d44a29c2fbdfab5d5bbe4
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spelling	oai:doaj.org-article:83f02438365d44a29c2fbdfab5d5bbe42021-11-25T18:20:34ZSex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study10.3390/metabo111107382218-1989https://doaj.org/article/83f02438365d44a29c2fbdfab5d5bbe42021-10-01T00:00:00Zhttps://www.mdpi.com/2218-1989/11/11/738https://doaj.org/toc/2218-1989Steroid 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-B1402. 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.Janne PottKatrin HornRobert ZeidlerHolger KirstenPeter AhnertJürgen KratzschMarkus LoefflerBerend IsermannUta CeglarekMarkus ScholzMDPI AGarticlesteroid hormonessexual dimorphismgenome-wide association analysisMendelian randomizationcoronary artery diseaseobesityMicrobiologyQR1-502ENMetabolites, Vol 11, Iss 738, p 738 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	steroid hormones sexual dimorphism genome-wide association analysis Mendelian randomization coronary artery disease obesity Microbiology QR1-502
spellingShingle	steroid hormones sexual dimorphism genome-wide association analysis Mendelian randomization coronary artery disease obesity Microbiology QR1-502 Janne Pott Katrin Horn Robert Zeidler Holger Kirsten Peter Ahnert Jürgen Kratzsch Markus Loeffler Berend Isermann Uta Ceglarek Markus Scholz Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study
description	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-B1402. 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.
format	article
author	Janne Pott Katrin Horn Robert Zeidler Holger Kirsten Peter Ahnert Jürgen Kratzsch Markus Loeffler Berend Isermann Uta Ceglarek Markus Scholz
author_facet	Janne Pott Katrin Horn Robert Zeidler Holger Kirsten Peter Ahnert Jürgen Kratzsch Markus Loeffler Berend Isermann Uta Ceglarek Markus Scholz
author_sort	Janne Pott
title	Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study
title_short	Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study
title_full	Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study
title_fullStr	Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study
title_full_unstemmed	Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study
title_sort	sex-specific causal relations between steroid hormones and obesity—a mendelian randomization study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/83f02438365d44a29c2fbdfab5d5bbe4
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Sex-Specific Causal Relations between Steroid Hormones and Obesity—A Mendelian Randomization Study

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