Investigating the Causal Relationship Between Sleep Behaviors and Primary Open-Angle Glaucoma: A Bidirectional Two-Sample Mendelian Randomization Study

Figures & data

Figure 1 Workflow of bidirectional Mendelian randomization analysis demonstrating causality between sleep-related behaviors and POAG. Three principal assumptions of a valid genetic instrument for MR analysis. The dotted line and the “×” represent variables that are invalid once correlated with the outcome or potential confounders.

Abbreviations: POAG, primary open-angle glaucoma; IVW, inverse variance weighted; MR-RAPS, MR robust adjusted profile score; MR-PRESSO, MR pleiotropy residual sum and outlier; BMI, body mass index.

Table 1 Detailed Information on Included Traits in this Study

Traits	Dataset	Consortium	Sample size	Case	Control	Population	PMID
Chronotype	ukb-b-4956	MRC-IEU	413343	–	–	European	–
Getting up in the morning	ukb-b-2772	MRC-IEU	461658	–	–	European	–
Sleep duration	ukb-b-4424	MRC-IEU	460099	–	–	European	–
Nap during the day	ukb-b-4616	MRC-IEU	462400	–	–	European	–
Insomnia	ukb-b-3957	MRC-IEU	462341	–	–	European	–
Daytime dozing/narcolepsy	ukb-b-5776	MRC-IEU	460913	–	–	European	–
Snoring	ukb-b-17,400	MRC-IEU	430438	270,007	160,431	European	–
OSA	–	–	362,638	25,008	337,630	European	36,525,587
POAG	GCST90011767	GWAS Catalog	192,702	15,229	177,473	European	33,627,673
	Finngen-public-data-r8	FinnGen	333,019	6585	326,434	European	–

Abbreviations: OSA, obstructive sleep apnea; POAG, primary open-angle glaucoma.

Table 2 Mendelian Randomization Positive Results and Heterogeneity Analysis for Effect of Genetically Predicted Sleep Related Behaviors on POAG

Method	No. of SNPs	MR Analysis			Heterogeneity Test			P-Intercept for MR-Egger	P-Global
		OR	95% CI	P	Cochran’s Q	I^2	P
Getting up in morning
IVW	66	1.78	1.29–2.46	4.33×10^−4	90.60	28.25%	0.020
Weighted median	66	1.71	1.08–2.72	0.023
Maximum likelihood	66	1.82	1.31–2.52	3.51×10^−4	90.21	27.94%	0.021
MR-PRESSO	66	1.82	1.31–2.52	3.52×10^−4					0.72
MR-Egger	66	1.11	0.28–4.42	0.879	89.92	28.82%	0.018	0.489
MR-RAPS	66	1.81	1.31–2.52	3.75×10^−4
Radial MR	66	1.81	1.32–2.50	4.04×10^−3	90.60	28.25%	0.020
Sleep duration
IVW	58	1.66	1.18–2.34	3.38×10^−3	87.68	34.99%	0.006
Weighted median	58	1.48	0.88–2.49	0.141
Maximum likelihood	58	1.70	1.20–2.40	2.93×10^−3	87.52	34.87%	0.006
MR-PRESSO	58	1.70	1.20–2.40	2.93×10^−3					0.39
MR-Egger	58	0.55	0.12–2.53	0.447	84.38	33.64%	0.008	0.145
MR-RAPS	58	1.69	1.20–2.40	2.86×10^−3
Radial MR	58	1.69	1.21–2.39	0.022	87.68	34.99%	0.006

Abbreviations: IVW, inverse variance weighted; MR, mendelian randomization; MR-PRESSO, MR-pleiotropy residual sum and outlier; No, number; SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.