MR-Egger plot with IVW, weighted median, and weighted mode lines for pleiotropy investigation and estimate comparison; variants used for instrumental analysis are independent SNPs (n = 274) constructing the large LDL-C IV. The results of per LDL-C-lowering allele have been coded so that trends correspond to the effects on frailty expected from the lowering of the biomarker. MR, Mendelian Randomization; IVW, inverse-variance weighted; LDL-C, low-density lipoprotein cholesterol; SNP, single-nucleotide polymorphism; IV, instrumental variable; FI, frailty index; CI, confidence interval.