Table 3.

Association between two lead genome-wide significant SNPs and risk of fracture (n=4285)

SNP ID	Genotype	No of participants with fracture / person-years	Multivariable Model 1		Multivariable Model 2		Multivariable Model 3
			Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value	Hazard ratio (95% CI)	P-value
Fracture
rs10822163	CC	122/4614	1.00 (ref)		1.00 (ref)		1.00 (ref)
	GaC	213/8646	0.92 (0.74, 1.15)	0.47	0.88 (0.70, 1.10)	0.25	0.86 (0.69, 1.08)	0.20
	GaGa	94/3636	0.96 (0.73, 1.25)	0.74	0.93 (0.71, 1.22)	0.61	0.96 (0.73, 1.26)	0.77
rs727428	CC	142/5118	1.00 (ref)		1.00 (ref)		1.00 (ref)
	TaC	205/8243	0.89 (0.72, 1.11)	0.30	0.93 (0.75, 1.15)	0.49	0.96 (0.77, 1.19)	0.69
	TaTa	82/3534	0.82 (0.63, 1.08)	0.17	0.84 (0.64, 1.10)	0.21	0.85 (0.65, 1.13)	0.27
Minimal trauma fracture
rs10822163	CC	117/4623	1.00 (ref)		1.00 (ref)		1.00 (ref)
	GaC	170/8655	0.77 (0.61, 0.98)	0.03	0.73 (0.57, 0.93)	0.01	0.73 (0.57, 0.93)	0.01
	GaGa	85/3639	0.91 (0.69, 1.20)	0.51	0.88 (0.67, 1.17)	0.38	0.92 (0.69, 1.22)	0.56
rs727428	CC	112/5127	1.00 (ref)		1.00 (ref)		1.00 (ref)
	TaC	186/8252	1.02 (0.81, 1.29)	0.85	1.06 (0.84, 1.34)	0.63	1.09 (0.85, 1.38)	0.50
	TaTa	74/3539	0.94 (0.70, 1.26)	0.68	0.95 (0.71, 1.27)	0.73	0.96 (0.71, 1.29)	0.77

SNP: single nucleotide polymorphism; CI: confidence interval; ^aDenotes the effect allele

Model 1: Adjusted for the top 10 genetic PCs; Model 2: Model 1 + age and body mass index; Model 3: Model 2 + alcohol consumption, smoking, diabetes, impaired renal function, treatment allocation (aspirin/placebo), medication affecting bone structure or mineralization, and high-density lipoprotein cholesterol