Results
Education
Our results showed significant inverse association of genetically
determined years of education with overall OC (odds ratio [OR], 0.8
[95% CI, 0.72–0.89]) (Fig. 2A ). Suggestive associations
were also observed for the protective effect of education attainment on
the subtypes of LMSOC (OR, 0.64 [95% CI, 0.48–0.84]), HGSOC (OR,
0.81 [95% CI, 0.72–0.92]), IMOC (OR, 0.68 [95% CI,
0.51–0.92]), LGSOC (OR, 0.67 [95% CI, 0.46–0.98]), and EOC (OR,
0.8 [95% CI, 0.65–0.99]). The inverse associations were persistent
in the weighted median and maximum likelihood mode. Although there was
inconsistency in the MR-Egger method, the MR-Egger test for pleiotropy
indicated that no significant pleiotropy was present. After removing
outliers in the MR-PRESSO analysis, the association of education with
all OC and OC subtypes persisted and the P value for the
distortion test were above 0.05 (Table S2 ). Most of the
associations for education and OC subtypes persisted and attenuated
slightly after multivariable adjustment (Table 2 ).
Coffee or tea consumption
There were limited data supporting associations of genetically predicted
coffee, or tea consumption with overall OC risk (Fig. 2B-C ).
However, higher genetically predicted coffee and tea consumption were
both positively associated with the endometrioid subtype. The ORs of EOC
were 1.70 [95% CI, 1.18–2.44]) for genetically predicted 50%
increase in coffee consumption (Fig. 2B ), and 1.84 [95% CI,
1.10–3.07]) for genetically predicted 50% increase in tea
consumption (Fig. 2C ). The positive association between coffee
consumption and EOC was also replicated in the sensitivity analyses
including the weighted median and maximum likelihood mode, although with
wider CI in the MR-Egger method (Table S3 ). For tea
consumption, the positive association was persistent in the weighted
median method, albeit there was some inconsistency in effect estimates
of other sensitivity analyses (Table S4 ). The association
between coffee or tea consumption and EOC did not remain after adjusting
for BMI (Table 2 ).
Relative fat intake and BMI
The results indicated that a higher relative fat intake causally
increases the risk of HGSOC (OR, 1.85 [95% CI, 1.06, 3.22]), but
reduces the risk of EOC (OR, 0.3 [95% CI, 0.11, 0.86])
(Fig. 2D ). The associations remained consistent in the maximum
likelihood mode, albeit with wider CI in the weighted median and
MR-Egger method (Table S5 ). After adjustment for BMI, the
association between fat intake and HGSOC attenuated greatly. However,
the protective effect of fat intake on EOC was not affected by BMI
(Table 2 ).
Genetic predisposition to higher BMI was significantly associated with
an increased risk of LMSOC (OR, 1.44 [95% CI 1.18–1.77])
(Fig. 2E ). The positive association was consistent in the
further analyses including weighted median, MR-Egger, and Maximum
Likelihood, suggesting little evidence for pleiotropy and potential
violations of instrumental variable assumptions (Table S6 ). A
suggestive association was also found between BMI and the EOC (OR, 1.27
[95% CI 1.07–1.50]). The effect estimate was persistent when
performing MR-Egger and maximum likelihood and was slightly attenuated
when employing weighted median mode estimators. In addition, a
borderline association was observed between BMI and LMMOC in IVW (OR,
1.29 [95% CI 1.01–1.66]) and maximum likelihood mode. Although no
statistically significant association was observed between BMI and all
OC, sensitive analysis indicated a suggestive association (Table
S6 ).
Smoking
Despite null associations between smoking initiation and risk of OC
subtypes (Fig. 2I and Table S10 ), genetic liability to
lifetime smoking index showed a suggestive association with an increased
risk of overall OC (OR, 1.23 [95% CI 1.04–1.46]), HGSOC (OR, 1.25
[95% CI 1.02–1.53]) and EOC (OR, 1.51 [95% CI 1.01–2.26])
histotypes (Fig. 2J) . The positive associations remained
consistent in the maximum likelihood mode, albeit with wider CI in the
weighted median and MR-Egger method (Table S11 ).
Physical activities, alcohol drinking, sleep duration, and insomnia
Among other lifestyle factors, there were no associations to be found
for physical activities (Fig. 2F-H) , alcohol drinking
(Fig. 2K) , sleep duration (Fig. 2L) , or insomnia
(Fig. 2M) with any type of OC in the primary analysis or the
sensitivity analyses (Table S7-9 , S12-14 ).