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Article: The role of cortisol in ischemic heart disease, ischemic stroke, type 2 diabetes, and cardiovascular disease risk factors: a bi-directional Mendelian randomization study

TitleThe role of cortisol in ischemic heart disease, ischemic stroke, type 2 diabetes, and cardiovascular disease risk factors: a bi-directional Mendelian randomization study
Authors
KeywordsCortisol
Cardiovascular disease
Diabetes
Risk factors
Mendelian randomization
Issue Date2020
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcmed/
Citation
BMC Medicine, 2020, v. 18 n. 1, p. article no. 363 How to Cite?
AbstractBackground: Cortisol, a steroid hormone frequently used as a biomarker of stress, is associated with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). To clarify whether cortisol causes these outcomes, we assessed the role of cortisol in ischemic heart disease (IHD), ischemic stroke, T2DM, and CVD risk factors using a bi-directional Mendelian randomization (MR) study. Methods: Single nucleotide polymorphisms (SNPs) strongly (P < 5 × 10−6) and independently (r2 < 0.001) predicting cortisol were obtained from the CORtisol NETwork (CORNET) consortium (n = 12,597) and two metabolomics genome-wide association studies (GWAS) (n = 7824 and n = 2049). They were applied to GWAS of the primary outcomes (IHD, ischemic stroke and T2DM) and secondary outcomes (adiposity, glycemic traits, blood pressure and lipids) to obtain estimates using inverse variance weighting, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Conversely, SNPs predicting IHD, ischemic stroke, and T2DM were applied to the cortisol GWAS. Results: Genetically predicted cortisol (based on 6 SNPs from CORNET; F-statistic = 28.3) was not associated with IHD (odds ratio (OR) 0.98 per 1 unit increase in log-transformed cortisol, 95% confidence interval (CI) 0.93–1.03), ischemic stroke (0.99, 95% CI 0.91–1.08), T2DM (1.00, 95% CI 0.96–1.04), or CVD risk factors. Genetically predicted IHD, ischemic stroke, and T2DM were not associated with cortisol. Conclusions: Contrary to observational studies, genetically predicted cortisol was unrelated to IHD, ischemic stroke, T2DM, or CVD risk factors, or vice versa. Our MR results find no evidence that cortisol plays a role in cardiovascular risk, casting doubts on the cortisol-related pathway, although replication is warranted.
Persistent Identifierhttp://hdl.handle.net/10722/308166
ISSN
2023 Impact Factor: 7.0
2023 SCImago Journal Rankings: 2.711
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKwok, MK-
dc.contributor.authorKawachi, I-
dc.contributor.authorRehkopf, D-
dc.contributor.authorSchooling, CM-
dc.date.accessioned2021-11-12T13:43:25Z-
dc.date.available2021-11-12T13:43:25Z-
dc.date.issued2020-
dc.identifier.citationBMC Medicine, 2020, v. 18 n. 1, p. article no. 363-
dc.identifier.issn1741-7015-
dc.identifier.urihttp://hdl.handle.net/10722/308166-
dc.description.abstractBackground: Cortisol, a steroid hormone frequently used as a biomarker of stress, is associated with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). To clarify whether cortisol causes these outcomes, we assessed the role of cortisol in ischemic heart disease (IHD), ischemic stroke, T2DM, and CVD risk factors using a bi-directional Mendelian randomization (MR) study. Methods: Single nucleotide polymorphisms (SNPs) strongly (P < 5 × 10−6) and independently (r2 < 0.001) predicting cortisol were obtained from the CORtisol NETwork (CORNET) consortium (n = 12,597) and two metabolomics genome-wide association studies (GWAS) (n = 7824 and n = 2049). They were applied to GWAS of the primary outcomes (IHD, ischemic stroke and T2DM) and secondary outcomes (adiposity, glycemic traits, blood pressure and lipids) to obtain estimates using inverse variance weighting, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Conversely, SNPs predicting IHD, ischemic stroke, and T2DM were applied to the cortisol GWAS. Results: Genetically predicted cortisol (based on 6 SNPs from CORNET; F-statistic = 28.3) was not associated with IHD (odds ratio (OR) 0.98 per 1 unit increase in log-transformed cortisol, 95% confidence interval (CI) 0.93–1.03), ischemic stroke (0.99, 95% CI 0.91–1.08), T2DM (1.00, 95% CI 0.96–1.04), or CVD risk factors. Genetically predicted IHD, ischemic stroke, and T2DM were not associated with cortisol. Conclusions: Contrary to observational studies, genetically predicted cortisol was unrelated to IHD, ischemic stroke, T2DM, or CVD risk factors, or vice versa. Our MR results find no evidence that cortisol plays a role in cardiovascular risk, casting doubts on the cortisol-related pathway, although replication is warranted.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmcmed/-
dc.relation.ispartofBMC Medicine-
dc.rightsBMC Medicine. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCortisol-
dc.subjectCardiovascular disease-
dc.subjectDiabetes-
dc.subjectRisk factors-
dc.subjectMendelian randomization-
dc.titleThe role of cortisol in ischemic heart disease, ischemic stroke, type 2 diabetes, and cardiovascular disease risk factors: a bi-directional Mendelian randomization study-
dc.typeArticle-
dc.identifier.emailKwok, MK: maggiek@hku.hk-
dc.identifier.emailSchooling, CM: cms1@hkucc.hku.hk-
dc.identifier.authorityKwok, MK=rp02051-
dc.identifier.authoritySchooling, CM=rp00504-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s12916-020-01831-3-
dc.identifier.pmid33243239-
dc.identifier.pmcidPMC7694946-
dc.identifier.scopuseid_2-s2.0-85096666952-
dc.identifier.hkuros329795-
dc.identifier.volume18-
dc.identifier.issue1-
dc.identifier.spagearticle no. 363-
dc.identifier.epagearticle no. 363-
dc.identifier.isiWOS:000595745600001-
dc.publisher.placeUnited Kingdom-

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