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

Table 1 Association of genetically predicted cortisol (P value< 5 × 10⁻⁶ and r² < 0.001) based on 3 separate data sources (CORtisol NETwork (CORNET) consortium, Shin GWAS, and Long GWAS) with ischemic heart disease (IHD) based on the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (1000 Genomes) with replication based on the UK Biobank using Mendelian randomization (MR) with different methods

Exposure sources	Outcome sources	SNPs	F-statistic	Method	Odds ratio	95% CI		P value	IVW		MR-Egger
Exposure sources	Outcome sources	SNPs	F-statistic	Method	Odds ratio	95% CI		P value	Cochran’s Q-statistic	P value	Intercept P value	I²
CORNET 2014	1000 Genomes	6	28.3	IVW	0.98	0.93	1.03	0.42	2.18	0.82
				WM	1.00	0.93	1.07	0.95
				MR-Egger	0.98	0.90	1.06	0.63			0.96	81.5%
				MR-PRESSO	0.98	0.93	1.02	0.28
	UK Biobank	6	28.3	IVW	0.99	0.93	1.05	0.71	2.29	0.81
				WM	0.99	0.92	1.07	0.82
				MR-Egger	0.99	0.89	1.10	0.85			0.96	71.3%
				MR-PRESSO	0.99	0.94	1.04	0.61
Shin GWAS 2014	1000 Genomes	5	23.9	IVW	0.74	0.47	1.17	0.19	4.52	0.34
				WM	0.78	0.45	1.35	0.37
				MR-Egger	0.84	0.32	2.20	0.72			0.77	35.3%
				MR-PRESSO	0.74	0.39	1.41	0.26
	UK Biobank	5	23.9	IVW	0.96	0.56	1.67	0.89	6.21	0.18
				WM	1.09	0.61	1.95	0.76
				MR-Egger	1.58	0.58	4.28	0.37			0.25	9.3%
				MR-PRESSO	0.96	0.44	2.10	0.90
Long GWAS 2017	1000 Genomes	18	14.9	IVW	1.02	0.99	1.05	0.18	21.43	0.21
				WM	1.01	0.98	1.05	0.44
				MR-Egger	1.02	0.96	1.09	0.47			0.91	0%
				MR-PRESSO	1.02	0.99	1.05	0.20
	UK Biobank	18	14.9	IVW	0.99	0.96	1.01	0.31	15.35	0.57
				WM	0.99	0.95	1.03	0.57
				MR-Egger	1.00	0.94	1.05	0.89			0.70	0%
				MR-PRESSO	0.99	0.96	1.01	0.30

Abbreviations: CI confidence interval, IVW inverse variance weighting, MR Mendelian randomization, SNP single nucleotide polymorphism, WM weighted median

ISSN: 1741-7015