Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis

Table 1 Details of the instruments used for exposures

Exposure	GWAS	Sample size	Number of SNPs	R²	F-statistic	Sex specificity
Adult BMI	Yengo et al. [41]	681,275	507	0.078	57,847	Combined
LDL cholesterol	Willer et al. [33]	188,577	81	0.182	15,002	Combined
HDL cholesterol	Willer et al. [33]	188,577	89	0.055	10,978	Combined
Triglyceride	Willer et al. [33]	188,577	55	0.052	9811	Combined
Total serum cholesterol	Willer et al. [33]	188,577	88	0.063	12,696	Combined
Glucose	Neale et al. [35]	361,194	109	0.036	11,776	Female
Fasting insulin (unadjusted for BMI)	Lagou et al. [42]	98,210	14	0.005	523	Combined
Fasting insulin (adjusted for BMI)	Chen et al. [43]	150,571	14	0.006	865	Combined
IGF-1 (cis and trans variants)	Sinnott-Armstrong et al. [36]	358,072	413	0.036	13,367	Combined
IGF-1 (cis variants)	Larsson et al. [44]	358,072	1	0.002	814	Combined
IL-6	Georgakis et al. [37]	204,402	7	0.004	911	Combined
Adiponectin (cis and trans variants)	Locke et al. [45]	14,172	3	0.023	328	Combined
Adiponectin (cis variants)	Locke et al. [45]	14,172	3	0.023	334	Combined
Leptin	Folkersen et al. [46]	30,931	1	0.001	34	Combined
CRP (cis and trans variants)	Ligthart et al. [40]	204,402	45	0.035	7414	Combined
CRP (cis variants)	C-Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC) [47]	105,476	4	0.010	1030	Combined
Total testosterone	Ruth et al. [28]	230,454	131	0.052	10,103	Female
Bioavailable testosterone	Ruth et al. [28]	188,507	147	0.054	10,599	Female
SHBG	Ruth et al. [28]	189,473	215	0.122	26,286	Female

BMI is scaled to an SD increase (4.7 kg/m²). For the analysis involving the plasma proteome, due to the requirement of increased statistical power in order to overcome the multiple testing burden, alternative summary genetic association data for BMI were obtained from a genome-wide association study of 681,275 individuals of European ancestry (note that this summary genetic data could not be used for other analyses due to substantial overlap of participants with summary genetic data of other traits) [41]. The CRP GWAS included some individuals of non-European ancestry and adjusted for ancestry where applicable. BMI body mass index, LDL low-density lipoprotein, HDL high-density lipoprotein, IGF-1 insulin-like growth factor-1, IL-6 interleukin-6, CRP C-reactive protein, SHBG sex hormone-binding globulin, LD linkage disequilibrium. For instrument construction of IGF-1 (cis and trans variants), a P value of 5 × 10⁻⁶ was used

ISSN: 1741-7015