Study overview
To implement MR, we integrated summary statistics (Table 1) from various genome-wide association (GWA) studies. Figure 1 contains an overview of our approach. First, we started by integrating the GWA studies for circulating metabolites (using metabolite quantitative trait loci, metQTLs)4,21 and healthspan22. With these integrated data, we performed an MR screen of 103 circulating nuclear-magnetic resonance (NRM) metabolites (sample sizes up to 24,925) and examined them in relation to healthspan (sample size = 300,447). This metabolite screen revealed that APOB and lipids containing LDL shorten healthspan. Next, we replicated these findings using larger GWA studies of APOB (sample size = 439,214) and LDL (sample size = 440,546) from the UK Biobank (UKBB) and performed a multivariable MR analysis to assess the direct effects of APOB and LDL on healthspan,…
