PMID- 33243239
OWN - NLM
STAT- MEDLINE
DCOM- 20210211
LR  - 20240330
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 18
IP  - 1
DP  - 2020 Nov 27
TI  - The role of cortisol in ischemic heart disease, ischemic stroke, type 2 diabetes, 
      and cardiovascular disease risk factors: a bi-directional Mendelian randomization 
      study.
PG  - 363
LID - 10.1186/s12916-020-01831-3 [doi]
LID - 363
AB  - BACKGROUND: 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 x 10(-6)) and 
      independently (r(2) < 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.
FAU - Kwok, Man Ki
AU  - Kwok MK
AD  - School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong 
      Kong, 1/F, Patrick Manson Building (North Wing), 7 Sassoon Road, Hong Kong 
      Special Administrative Region, China.
FAU - Kawachi, Ichiro
AU  - Kawachi I
AD  - Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public 
      Health, Boston, MA, USA.
FAU - Rehkopf, David
AU  - Rehkopf D
AD  - Department of Medicine, Stanford University, Stanford, CA, USA.
FAU - Schooling, Catherine Mary
AU  - Schooling CM
AUID- ORCID: 0000-0001-9933-5887
AD  - School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong 
      Kong, 1/F, Patrick Manson Building (North Wing), 7 Sassoon Road, Hong Kong 
      Special Administrative Region, China. cms1@hku.hk.
AD  - City University of New York Graduate School of Public Health and Health Policy, 
      New York, USA. cms1@hku.hk.
LA  - eng
GR  - 02160107/Health and Medical Research Fund/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201127
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 0 (Biomarkers)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Biomarkers/*blood
MH  - Cardiovascular Diseases/*etiology
MH  - Diabetes Mellitus, Type 2/*etiology
MH  - Female
MH  - Humans
MH  - Hydrocortisone/pharmacology/*therapeutic use
MH  - Ischemic Stroke/*etiology
MH  - Male
MH  - Mendelian Randomization Analysis/*methods
MH  - Middle Aged
MH  - Myocardial Ischemia/*etiology
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Risk Factors
PMC - PMC7694946
OTO - NOTNLM
OT  - Cardiovascular disease
OT  - Cortisol
OT  - Diabetes
OT  - Mendelian randomization
OT  - Risk factors
COIS- The authors declare that they have no competing interests.
EDAT- 2020/11/28 06:00
MHDA- 2021/02/12 06:00
PMCR- 2020/11/27
CRDT- 2020/11/27 05:30
PHST- 2020/06/22 00:00 [received]
PHST- 2020/10/28 00:00 [accepted]
PHST- 2020/11/27 05:30 [entrez]
PHST- 2020/11/28 06:00 [pubmed]
PHST- 2021/02/12 06:00 [medline]
PHST- 2020/11/27 00:00 [pmc-release]
AID - 10.1186/s12916-020-01831-3 [pii]
AID - 1831 [pii]
AID - 10.1186/s12916-020-01831-3 [doi]
PST - epublish
SO  - BMC Med. 2020 Nov 27;18(1):363. doi: 10.1186/s12916-020-01831-3.