Causal relationship between affect disorders and endometrial cancer: a Mendelian randomisation study

Figures & data

Table 1. Summary of GWAS^a statistics information.

Author, year	Setting	Trait	Sample size	Ancestry
Meier et al.2019	Integrative Psychiatric Research	Lifetime diagnoses of anxiety and stress-related disorders	31,880(Male 44.4%)	European
Howard et al.2019	23andMe, UK Biobank, PGC^b	Major depressive disorder	807,753^c	European
O’Mara et al.2018	ECAC, E2C2, UK Biobank^d	Endometrial cancer^e	121,885(Male 0%)	European
FinnGen	FinnGen	Polycystic ovary syndrome	118,228^b	European
Neale	Neale Lab	Body mass index	336,107	European
Ben Elsworth	MRC-IEU	Age at menopause (last menstrual period)	143,819	European
Wood et al. 2016	UK Biobank	Type 2 diabetes	120,286	European

^aGWAS, genome-wide association studies; ^bPGC, Psychiatric Genomics Consortium; ^cRatio of males and females not available in the original literature; ^dECAC, Endometrial Cancer Association Consortium; E2C2, the Epidemiology of Endometrial Cancer Consortium; ^eEndometrial cancer includes all histologies, endometrioid histology, and nonendometrioid histology.

Table 2. Results of horizontal pleiotropy assesment by MR-PRESSO method.

Exposure	Outcome	Estimate	Sd	p-Value
ASRDs	EC(EH)	0.002	0.007	0.78
	EC(NEH)	−0.010	0.018	0.61
	EC(AH)	0.002	0.007	0.82
MDD	EC(EH)	0.150	0.117	0.205
	EC(NEH)	0.099	0.239	0.678
	EC(AH)	0.036	0.092	0.70

Sd: standard deviation; ASRDs: anxiety and stress-related disorders; EC: endometrial cancer; EH: endometrioid histology; NEH: nonendometrioid histology; MDD: major depressive disorder; AH: all histology.

Table 3. Single-variable MR results of ASRDs and MDD on the risk of three subtypes of EC.

Exposure	Outcome	Method	Effect	SE	95% CI	p Value
ASRDs	EC(EH)	IVW	0.002	0.007	−0.013–0.016	0.84
	EC(EH)	MR-Egger	0.013	0.076	−0.136–0.162	0.865
	EC(EH)	Weighted median	0.002	0.01	−0.016–0.021	0.793
ASRDs	EC(NEH)	IVW	−0.009	0.018	−0.044–0.025	0.595
	EC(NEH)	MR-Egger	0.142	0.337	−0.519–0.802	0.674
	EC(NEH)	Weighted median	−0.003	0.023	−0.048–0.042	0.9
ASRDs	EC(AH)	IVW	0.002	0.008	−0.013–0.017	0.794
	EC(AH)	MR-Egger	0.161	0.049	0.064–0.258	0.001
	EC(AH)	Weighted median	0	0.008	−0.016–0.017	0.964
MDD	EC(EH)	IVW	0.004	0.002	0–0.008	0.047*
	EC(EH)	MR-Egger	−0.253	0.374	−0.987–0.48	0.498
	EC(EH)	Weighted median	0.004	0.003	−0.002–0.01	0.176
MDD	EC(NEH)	IVW	−0.001	0.005	−0.01–0.009	0.9
	EC(NEH)	MR-Egger	0.588	0.791	−0.962–2.138	0.457
	EC(NEH)	Weighted median	0	0.007	−0.013–0.014	0.983
MDD	EC(AH)	IVW	0.001	0.002	−0.002–0.005	0.443
	EC(AH)	MR-Egger	−0.691	0.284	−1.248–−0.134	0.015*
	EC(AH)	Weighted median	0.003	0.002	−0.002–0.008	0.191

MR: Mendelian randomisation; SE: Standard Error; CI: confidence interval; ASRDs: anxiety and stress-related disorders; EC: endometrial cancer; EH: endometrioid histology; IVW: inverse variance weighting; NEH: nonendometrioid histology; MDD: major depressive disorder; AH: all histology; *: the p value is less than 0.05, which is statistically significant.

Table 4. Multivariate Mendelian randomisation results of the three pathology types.

	EC(EH)^a			EC(NEH)^b			EC(AH)^x
Exposure	NO. SNPs^d	effect	p	NO. SNPs	effect	p	NO. SNPs	effect	p
PCOS^e	319	−0.04	0.08	319	0.04	0.39	319	−0.02	0.31
T2D^f	319	0.04	0.14	319	0.11	0.06	319	0.05	0.05
MDD^g	319	−0.09	0.53	319	0.21	0.47	319	−0.14	0.25
BMI^h	319	0.57	<0.01	319	0.44	<0.01	319	0.55	<0.01
AAM^i	319	0.21	<0.01	319	0.34	0.01	319	0.20	<0.01

^aEC, endometrial cancer; EH, endometrioid histology; ^bNEH, nonendometrioid histology; ^cAH, all histology; ^dNumber of single nucleotide polymorphisms; ^ePolycystic ovary syndrome; ^fType 2 diabetes; ^gMajor Depression Disorder; ^hBody mass index; ⁱAge at menopause.

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Data availability statement

The data used in this study are publicly available and both the data and the methods of acquisition have been provided in Appendix A.