Table 1.
IVW estimates for the FI effect of life-long lowering of LDL-C concentrations indicated by the constructed IVs; independent individuals were involved by randomly dropping the related ones reaching a kinship threshold of 0.1768.
| IV set (number of SNPs) | Main analyses (n = 378,161) |
Modified FI excluding cardiometabolic deficit items (n = 378,161) |
FI in participants ≥60 years (n = 167,013) |
|||
|---|---|---|---|---|---|---|
| Effect (95% CI) | p | Effect (%95 CI) | p | Effect (%95 CI) | p | |
| Large (274) | −0.23 (−0.27, −0.18) | <0.0005 | −0.26 (−0.30, −0.21) | <0.0005 | −0.40 (−0.46, −0.33) | <0.0005 |
| Small (50) | −0.23 (−0.32, −0.14) | <0.0005 | −0.27 (−0.37, −0.18) | <0.0005 | −0.37 (−0.50, −0.23) | <0.0005 |
| HMGCR (16) | −0.61 (−0.92, −0.30) | <0.0005 | −0.68 (−1.03, −0.34) | <0.0005 | −0.71 (−1.19, −0.23) | 0.004 |
| PCSK9 (34) | −0.14 (−0.30, 0.02) | 0.097 | −0.13 (−0.31, 0.05) | 0.159 | −0.22 (−0.48, 0.03) | 0.083 |
| NPC1L1 (24) | −0.40 (−0.89, 0.08) | 0.104 | −0.44 (−0.97, 0.10) | 0.107 | −0.65 (−1.40, 0.09) | 0.086 |
| APOB (30) | 0.06 (−0.08, 0.20) | 0.388 | 0.05 (−0.10, 0.20) | 0.521 | −0.09 (−0.30, 0.13) | 0.426 |
| APOC3 (19) | −0.58 (−0.98, −0.18) | 0.004 | −0.67 (−1.12, −0.23) | 0.003 | −0.64 (−1.26, −0.02) | 0.043 |
| LDLR (30) | −0.28 (−0.44, −0.13) | <0.0005 | −0.32 (−0.49, −0.15) | <0.0005 | −0.56 (−0.80, −0.32) | <0.0005 |
Bold indicates reaching statistical significance of P < .05. IVW, inverse-variance weighted; CI, confidence interval; LDL-C, low-density lipoprotein cholesterol level in serum; FI, frailty index; IV, instrumental variable; SNPs, single-nucleotide polymorphisms.