Stability of plasma metabolomics over 10 years among women

Abstract Background In epidemiological studies, samples are often collected long before disease onset or outcome assessment. Understanding the long-term stability of biomarkers measured in these samples is crucial. We estimated within-person stability over 10 years of metabolites and metabolite features (N=5938) in the Nurses’ Health Study (NHS): The primary dataset included 1880 women with 1184 repeated samples donated 10 years apart while the secondary dataset included 1456 women with 488 repeated samples donated 10 years apart. Methods We quantified plasma metabolomics using two liquid chromatography mass spectrometry platforms (lipids and polar metabolites) at the Broad Institute (Cambridge, MA). Intra-class correlations were used to estimate long-term stability (10 years) of metabolites and were calculated as the proportion of the total variability (within-person + between-person) attributable to between-person variability. Within-person variability was estimated among participants who donated two blood samples approximately 10 years apart while between-person variability was estimated among all participants. Results In the primary dataset, the median ICC was 0.43 (1 st quartile [Q1]: 0.36; 3 rd quartile [Q3]: 0.50) among known metabolites and 0.41 (Q1: 0.34; Q3: 0.48) among unknown metabolite features. The most stable (median ICCs: 0.54-0.57) metabolite classes were nucleosides, nucleotides and analogues, phosphatidylcholine plasmalogens, diglycerides, and cholesteryl esters. The least stable (median ICCs: 0.26-0.36) metabolite classes were lysophosphatidylethanolamines, lysophosphatidylcholines and steroid and steroid derivatives. Results in the secondary dataset were similar (Spearman correlation=0.87) to corresponding results in the primary dataset. Conclusion Within-person stability over 10 years is reasonable for lipid, lipid-related, and polar metabolites, and varies by metabolite class. Additional studies are required to estimate within-person stability over 10 years of other metabolites groups.