Table 2.
PheWAS results, PCSK9 variant R46L
| SNP | SNP effect | A potential safety signal OR should be: | Phenotype | Cases (n) | Controls (n) | OR (95% CI) | P-value | Case carriers (n) |
|---|---|---|---|---|---|---|---|---|
| R46L | LOF | >1 | Spina bifida | 34 | 25,268 | 5.90 (2.27–15.36) | 2.7×10−04 | 6 |
| R46L | LOF | >1 | Hypercholesterolemia | 3,840 | 14,560 | 0.68 (0.54–0.85) | 7.6×10−04 | 101 |
| R46L | LOF | >1 | Mixed hyperlipidemia* | 4,328 | 14,560 | 0.70 (0.57–0.87) | 1.3×10−03 | 114 |
| R46L | LOF | >1 | Fracture of ankle and foot* | 660 | 21864 | 1.76 (1.25–2.47) | 1.3×10−03 | 37 |
| R46L | LOF | >1 | Calcaneal spur; Exostosis NOS | 57 | 19642 | 3.43 (1.50–7.86) | 3.6×10−03 | 6 |
| R46L | LOF | >1 | Hyperlipidemia* | 9050 | 14560 | 0.79 (0.67–0.93) | 3.8×10−03 | 264 |
| R46L | LOF | >1 | Senile osteoporosis | 745 | 19123 | 1.52 (1.06–2.18) | 0.021 | 38 |
| R46L | LOF | >1 | Coronary atherosclerosis | 4960 | 18085 | 0.79 (0.65–0.97) | 0.025 | 134 |
| R46L | LOF | >1 | Fracture of foot* | 344 | 21864 | 1.69 (1.05–2.73) | 0.030 | 19 |
| R46L | LOF | >1 | Other forms of chronic heart disease | 999 | 18085 | 0.64 (0.42–0.98) | 0.042 | 23 |
| R46L | LOF | >1 | Fracture of vertebral column without mention of spinal cord injury | 617 | 21864 | 1.47 (1.01–2.15) | 0.047 | 29 |
Key: Bolded odds ratios indicate potential consequences of long-term natural PCKS9 inhibition; OR odds ratio; CI = confidence interval; LOF = loss-of-function. Note: R46L minor allele frequency is 0.01594 in the BioVU Exomechip population.
*
“Mixed hyperlipidemia” represents a subset of the “Hyperlipidemia” phenotype; “Fracture of foot” represents a subset of the “Fracture of ankle and foot” phenotype.