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

Kwok, Man Ki; Kawachi, Ichiro; Rehkopf, David; Schooling, Catherine Mary

doi:10.1186/s12916-020-01831-3

Table 4 Association of genetically predicted cortisol (P value< 5 × 10⁻⁶ and r² < 0.001) based on the CORtisol NETwork (CORNET) consortium, with cardiovascular disease (CVD) risk factors (adiposity based on the Genetic Investigation of Anthropometric Traits (GIANT), glycemic traits based on the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), blood pressure based on the UK Biobank, and lipids based on the Global Lipids Genetics Consortium (GLGC)) using Mendelian randomization (MR) with different methods

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

Outcomes	Sources	SNPs	F-statistic	Method	Mean difference	95% CI		P value	IVW		MR-Egger
Outcomes	Sources	SNPs	F-statistic	Method	Mean difference	95% CI		P value	Cochran’s Q-statistic	P value	Intercept P value	I²
Adiposity
BMI	GIANT	6	28.3	IVW	− 0.001	− 0.01	0.01	0.85	2.37	0.80
				WM	− 0.003	− 0.02	0.01	0.72
				MR-Egger	0.01	− 0.01	0.03	0.55			0.36	71.3%
				MR-PRESSO	− 0.001	− 0.01	0.01	0.80
WHR	GIANT	6	28.3	IVW	− 0.01	− 0.02	0.01	0.26	7.55	0.18
				WM	− 0.01	− 0.02	0.01	0.53
				MR-Egger	0.003	− 0.02	0.03	0.76			0.17	71.8%
				MR-PRESSO	− 0.01	− 0.03	0.01	0.31
Glycemic traits
HbA1c	MAGIC	6	28.3	IVW	− 0.01	− 0.03	0.01	0.46	5.89	0.32
				WM	− 0.005	− 0.03	0.02	0.72
				MR-Egger	0.004	− 0.03	0.04	0.80			0.39	27.6%
				MR-PRESSO	− 0.01	− 0.03	0.02	0.49
Glucose	MAGIC	6	28.3	IVW	0.02	− 0.004	0.05	0.10	4.64	0.46
				WM	0.02	− 0.02	0.05	0.31
				MR-Egger	0.04	− 0.004	0.08	0.08			0.33	73.1%
				MR-PRESSO	0.02	− 0.01	0.05	0.15
Insulin	MAGIC	6	28.3	IVW	0.01	− 0.02	0.04	0.45	3.12	0.68
				WM	0.01	− 0.02	0.05	0.51
				MR-Egger	0.01	− 0.04	0.05	0.77			0.82	73.1%
				MR-PRESSO	0.01	− 0.02	0.04	0.38
Blood pressure
Systolic BP	UK Biobank	6	28.3	IVW	0.01	− 0.03	0.04	0.71	21.11	0.001
				WM	− 0.002	− 0.02	0.02	0.86
				MR-Egger	− 0.03	− 0.06	− 0.003	0.03			0.001	71.5%
				MR-PRESSO^a	− 0.001	− 0.02	0.02	0.93
Diastolic BP	UK Biobank	6	28.3	IVW	0.001	− 0.03	0.03	0.93	12.87	0.02
				WM	0.01	− 0.01	0.03	0.52
				MR-Egger	− 0.02	− 0.06	0.01	0.18			0.07	71.5%
				MR-PRESSO	0.001	− 0.03	0.04	0.93
Lipids
Total Cholesterol	GLGC	6	28.3	IVW	− 0.02	− 0.06	0.01	0.21	5.39	0.37
				WM	− 0.04	− 0.08	0.01	0.12
				MR-Egger	− 0.04	− 0.11	0.02	0.20			0.48	74.7%
				MR-PRESSO	− 0.02	− 0.07	0.03	0.26
HDL-Cholesterol	GLGC	6	28.3	IVW	0.01	− 0.04	0.05	0.80	9.36	0.10
				WM	− 0.003	− 0.05	0.04	0.89
				MR-Egger	− 0.04	− 0.10	0.03	0.28			0.11	75.1%
				MR-PRESSO	0.01	− 0.06	0.07	0.81
LDL-Cholesterol	GLGC	6	28.3	IVW	− 0.03	− 0.07	0.003	0.07	4.20	0.52
				WM	− 0.04	− 0.09	0.005	0.08
				MR-Egger	− 0.04	− 0.10	0.02	0.19			0.78	75.4%
				MR-PRESSO	− 0.03	− 0.08	0.01	0.11
Triglycerides	GLGC	6	28.3	IVW	− 0.01	− 0.04	0.03	0.70	2.16	0.83
				WM	− 0.01	− 0.05	0.03	0.69
				MR-Egger	− 0.01	− 0.06	0.04	0.72			0.88	75.8%
				MR-PRESSO	− 0.01	− 0.04	0.02	0.59

Abbreviations: BP blood pressure, CI confidence interval, HDL high-density lipoprotein, LDL low-density lipoprotein, IVW inverse variance weighting, MR Mendelian randomization, SNP single nucleotide polymorphism, WM weighted median
^aMR-PRESSO estimate was obtained by excluding 1 outlier (rs6830)

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