Table 1 Association between age at menarche/age at menopause and CRC risk using MR analyses and sensitivity analyses

		GRS-based analyses^b						2-sample MR^f
		MR estimate^a		Adjusted by GRS-BMI^a,c		Restricted risk score^a,d		MR-Egger^b,e		Weighted median estimator^b
Variable (per year)	Cases/Controls	OR	95% CI	OR	95% CI	OR	95% CI	OR	95% CI	OR	95% CI
Age at menarche	12,944/10,741	0.98	0.95–1.02	0.99	0.95–1.02	0.99	0.95–1.03	0.99	0.83–1.17	1.00	0.90–1.11
Age at menopause	12,944/10,741	0.98	0.94–1.01	NA	NA	NA	NA	1.02	0.94–1.10	1.00	0.95–1.05
Time period of hormone exposure	12,944/10,741	0.99	0.97–1.02	0.99	0.97–1.02	0.99	0.97–1.01	0.97	0.93–1.01	1.00	0.95–1.05

BMI body mass index, CCFR Colon Cancer Family Registry, CI confidence interval, CORECT Colorectal Transdisciplinary study, GECCO Genetics and Epidemiology of Colorectal Cancer Consortium, GRS genetic risk score, MR Mendelian randomisation, NA not applicable, OR odds ratio per year, SNPs single-nucleotide polymorphisms, se standard error
^aLogistic regression model adjusted for age, study, and principal components of genetic ancestry
^bMeta-analysed estimate of GECCO/CORECT datasets (CCFR centres participated in GECCO or CORECT and were analysed as such)
^cAdditionally adjusted for a GRS for BMI out of 77 reported SNPs for BMI³⁶
^d42 BMI-associated SNPs were excluded from the age at menarche and time period of oestrogen exposure—risk scores
^eEstimate derived from the slope of MR-Egger
^fEstimates derived using summary statistics; se for calculation of CI obtained via bootstrapping

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