Table 1.
Effect of monogenic mutation or polygenic score on odds for extremely high or low LDL-C
| Extremely high LDL-C | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Ancestry | N total | N extreme | Monogenic carrier (Nextreme) | High polygenic score (Nextreme) | Monogenic carrier OR (95% CI) | Monogenic carrier P-value | Monogenic carrier PAF | High polygenic score OR (95% CI) | High polygenic score P-value | Top 5th percentile of polygenic score PAF |
| EA | 5910 | 284 | 5 | 64 | 10.92 (3.71, 32.14) | 1.4 × 10−5 | 1.60 | 7.65 (5.56, 10.52) | 5.7 × 10−36 | 19.6 |
| AA | 4380 | 217 | 7 | 29 | 7.43 (3.01, 18.35) | 1.4 × 10−5 | 2.79 | 3.2 (2.1, 4.89) | 6.7 × 10−8 | 9.2 |
| Extremely Low LDL-C | ||||||||||
| Ancestry | N total | N extreme | Monogenic carrier (Nextreme) | Low polygenic score ( N extreme ) | Monogenic carrier OR (95% CI) | Monogenic carrier P -value | Monogenic carrier PAF | Low polygenic score OR (95% CI) | Low polygenic score P -value | Bottom 5th percentile of polygenic score PAF |
| EA | 5910 | 286 | 6 | 82 | 21.73 (6.2, 76.15) | 1.5 × 10−6 | 2.00 | 10.38 (7.69, 14.02) | 1.5 × 10−52 | 25.9 |
| AA | 4380 | 218 | 11 | 32 | 13.83 (6.25, 30.62) | 9.4 × 10−11 | 4.68 | 3.7 (2.46, 5.58) | 3.9 × 10−10 | 10.7 |
Values are represented as OR [95% CI] for association with given trait. (b). Effect of monogenic mutation or polygenic score on LDL-C in mg/dl. Values are represented as beta [95% CI] in mg/dl for LDL-C. Multi-variable associations were performed with sex + age + age2 (effects not listed) with monogenic carrier status + high polygenic score using logistic regression. Polygenic risk score was derived from 2 million variants using LDpred. High polygenic score was defined as membership in the top 5th percentile of the ancestry-specific score distribution. AA, African American; EA, European American; SE, standard error.