PMID- 34822396
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240404
IS  - 2218-1989 (Print)
IS  - 2218-1989 (Electronic)
IS  - 2218-1989 (Linking)
VI  - 11
IP  - 11
DP  - 2021 Oct 28
TI  - Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian 
      Randomization Study.
LID - 10.3390/metabo11110738 [doi]
LID - 738
AB  - 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.
FAU - Pott, Janne
AU  - Pott J
AUID- ORCID: 0000-0002-5983-5331
AD  - Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, 
      University of Leipzig, 04107 Leipzig, Germany.
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
FAU - Horn, Katrin
AU  - Horn K
AUID- ORCID: 0000-0002-5307-6936
AD  - Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, 
      University of Leipzig, 04107 Leipzig, Germany.
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
FAU - Zeidler, Robert
AU  - Zeidler R
AD  - Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 
      University Hospital Leipzig, 04103 Leipzig, Germany.
FAU - Kirsten, Holger
AU  - Kirsten H
AUID- ORCID: 0000-0002-3126-7950
AD  - Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, 
      University of Leipzig, 04107 Leipzig, Germany.
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
FAU - Ahnert, Peter
AU  - Ahnert P
AUID- ORCID: 0000-0002-1771-0856
AD  - Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, 
      University of Leipzig, 04107 Leipzig, Germany.
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
FAU - Kratzsch, Jurgen
AU  - Kratzsch J
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
AD  - Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 
      University Hospital Leipzig, 04103 Leipzig, Germany.
FAU - Loeffler, Markus
AU  - Loeffler M
AD  - Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, 
      University of Leipzig, 04107 Leipzig, Germany.
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
FAU - Isermann, Berend
AU  - Isermann B
AUID- ORCID: 0000-0003-0714-6160
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
AD  - Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 
      University Hospital Leipzig, 04103 Leipzig, Germany.
FAU - Ceglarek, Uta
AU  - Ceglarek U
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
AD  - Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, 
      University Hospital Leipzig, 04103 Leipzig, Germany.
FAU - Scholz, Markus
AU  - Scholz M
AD  - Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, 
      University of Leipzig, 04107 Leipzig, Germany.
AD  - LIFE Research Center for Civilization Diseases, Medical Faculty, University of 
      Leipzig, 04103 Leipzig, Germany.
LA  - eng
GR  - 713-24120/European Regional Development Fund/
GR  - 14505/2470/Freistaat Sachsen/
GR  - HIMAG-108/Helmholtz Zentrum Munchen/
GR  - 01ZX1906B/Bundesministerium fur Bildung und Forschung/
PT  - Journal Article
DEP - 20211028
PL  - Switzerland
TA  - Metabolites
JT  - Metabolites
JID - 101578790
PMC - PMC8624973
OTO - NOTNLM
OT  - Mendelian randomization
OT  - coronary artery disease
OT  - genome-wide association analysis
OT  - obesity
OT  - sexual dimorphism
OT  - steroid hormones
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/26 06:00
MHDA- 2021/11/26 06:01
PMCR- 2021/10/28
CRDT- 2021/11/25 17:09
PHST- 2021/10/14 00:00 [received]
PHST- 2021/10/22 00:00 [revised]
PHST- 2021/10/26 00:00 [accepted]
PHST- 2021/11/25 17:09 [entrez]
PHST- 2021/11/26 06:00 [pubmed]
PHST- 2021/11/26 06:01 [medline]
PHST- 2021/10/28 00:00 [pmc-release]
AID - metabo11110738 [pii]
AID - metabolites-11-00738 [pii]
AID - 10.3390/metabo11110738 [doi]
PST - epublish
SO  - Metabolites. 2021 Oct 28;11(11):738. doi: 10.3390/metabo11110738.