Plasma metabolites were profiled at the Broad Institute (Cambridge, MA) using untargeted liquid chromatography tandem mass spectrometry methods as described previously (25 (link)). Briefly, two methods were applied for the measurement of circulating metabolites: 1) amines and polar metabolites that ionize in the positive ion mode were measured using an liquid chromatography-mass spectrometry (LC-MS) platform comprised of an Open Accela 1250 U-HPLC coupled with a Q Exactive hybrid quadrupole orbitrap mass spectrometer (Thermo Fisher Scinetific; Waltham, MA); 2) polar and non-polar lipids were measured using an LC-MS platform comprised of a Shimazu Nexera X2 U-HPLC coupled to an Exactive Plus orbitrap mass spectrometer (Thermo Fisher Scientific; Waltham, MA). We dropped unknown metabolites, metabolites with coefficient of variation (CV) higher than 25% or intraclass correlation coefficient (ICC) less than 0.4 as indicators of interassay reproducibility and within-person reproducibility, metabolites with undetectable levels in >10% of participants, and metabolites that could not be reasonably reproducible in samples with delayed processing in previous pilot tests (25 (link),26 (link)). Metabolite values below the detection limit were assigned a half value of detection limit.