Central Illustration.

A. Prevalence of a FH mutation amongst severely hypercholesterolemic individuals. B. Risk of coronary artery disease across LDL cholesterol and familial hypercholesterolemia mutation status categories. Odds ratios for CAD were calculated via logistic regression with adjustment for gender, cohort, and principal components of ancestry relative to a reference category of LDL cholesterol <130 mg/dl without a familial hypercholesterolemia (FH) mutation. Counts of CAD-free controls vs. CAD cases in each category are provided in Supplementary Table 6. P-value for mutation carriers vs. noncarriers across strata of LDL cholesterol < 0.0001. P-interaction between LDL cholesterol category and mutation status = 0.51