Fig. 2: Interplay of monogenic and polygenic risk for breast cancer.

a Risk of breast cancer by monogenic and polygenic strata (case-control study; n = 19,264). Carriers and noncarriers were stratified into three groups according to their polygenic score—low, intermediate, or high defined as the lowest quintile, the middle three quintiles, and the highest quintile of the polygenic score distribution, respectively. The odds ratio was assessed in a logistic regression model with age and the first four principal components of ancestry as covariates. Noncarriers with intermediate polygenic score served as the reference group. The black boxes indicate the adjusted odds ratio. The horizontal lines around the black boxes indicate the 95% confidence intervals. b Predicted odds ratio for breast cancer in each percentile (dots) of the polygenic score distribution for carriers (blue) and noncarriers (black) of hereditary breast and ovarian cancer variants in the cohort study derived from the UK Biobank (n = 26,597). Noncarriers with median polygenic score served as the reference group. c Predicted probability of coronary artery disease by age 75 years in each percentile (dots) of the polygenic score distribution for carriers (blue) and noncarriers (black) of hereditary breast and ovarian cancer variants in the cohort study derived from the UK Biobank (n = 26,597). The shaded area around the dots represents the 95% confidence interval. The horizontal dashed lines show the probability of disease for people with average polygenic risk score. HBOC hereditary breast and ovarian cancer. p-values in the figure were estimated by the Wald Test. Statistical significance was set at p < .05, and two-sided p values were used.