Table 3.

Association of polygenic risk score (PRS) with breast cancer risk and evaluation of confounding due to family history and density measures (adjusted PD and adjusted DA). All eight studies combined and subset to cohort/population-based studies. All models adjusted for age, 1/BMI, and study

Model	N case/N control	PRS OR (95% CI)	+Family history OR (95% CI)	+adjusted PD OR (95% CI)	+adjusted DA OR (95% CI)
Overall sample
Overall PRS (per 1 SD)	3628/5126	1.52 (1.45, 1.59)	1.52 (1.44, 1.59)	1.50 (1.42, 1.57)	1.50 (1.43, 1.58)
PRS quintile
1	349/1033	0.51 (0.44, 0.60)	0.51 (0.44, 0.61)	0.53 (0.45, 0.63)	0.53 (0.45, 0.63)
2	535/1008	0.80 (0.69, 0.93)	0.78 (0.67, 0.92)	0.80 (0.69, 0.94)	0.80 (0.69, 0.94)
3 (Ref)	687/1024	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)
4	887/1032	1.31 (1.14, 1.50)	1.31 (1.14, 1.51)	1.32 (1.14, 1.53)	1.33 (1.15, 1.53)
5	1170/1029	1.66 (1.45, 1.90)	1.65 (1.44, 1.90)	1.64 (1.43, 1.89)	1.65 (1.44, 1.91)
Cohort/population-based studies only
Overall PRS (per 1 SD)	2439/3895	1.56 (1.48, 1.66)	1.55 (1.47, 1.65)	1.54 (1.45, 1.63)	1.55 (1.46, 1.64)
PRS quintile
1	232/786	0.51 (0.42, 0.62)	0.51 (0.42, 0.62)	0.53 (0.43, 0.65)	0.53 (0.43, 0.64)
2	361/776	0.80 (0.66, 0.95)	0.79 (0.66, 0.94)	0.80 (0.67, 0.96)	0.80 (0.67, 0.96)
3 (Ref)	464/789	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)	1.00 (Ref)
4	589/793	1.30 (1.10, 1.53)	1.28 (1.08, 1.52)	1.29 (1.09, 1.54)	1.30 (1.10, 1.54)
5	793/751	1.79 (1.52, 2.11)	1.76 (1.50, 2.08)	1.76 (1.49, 2.08)	1.77 (1.50, 2.09)

Heterogeneity of PRS association by study: P = 0.84 for population based studies

PRS quintiles: quintile 1, − 1.411 to − 0.014; quintile 2, − 0.015 to 0.280; quintile 3, 0.281 to 0.542; quintile 4, 0.543 to 0.885; quintile 5, 0.886 to 2.583

SD standard deviation, CI confidence interval, Ref reference group, Adj adjusted