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. 2022 Sep 22;28(11):2309–2320. doi: 10.1038/s41591-022-01980-3

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 3 — a) Displayed are discriminative performances described by the C-index for UK Biobank and the four external validation cohorts, Whitehall II (WHII), Rotterdam Study (RS), Leiden Longevity Study (LLS), and the PROSPER trial (PROSPER). CPH models were trained on the metabolomic state model (MET) as fitted on UK Biobank and applied to each cohort, as well as on Age+Sex and Age+Sex+MET. The metabolomic state is predictive in the replication cohorts for all assessed endpoints. Dots indicate the median performance, while whiskers indicate the 95% confidence interval (CI) determined by bootstrapping over 1000 iterations. b) Age+Sex adjusted hazard ratios (HRs) for the metabolomic state in all five cohorts. A unit standard deviation increase in the metabolomic state corresponds to an HR increase in predicted risk. Statistical measures were derived from n = 6.117 (Whitehall II), n = 2949 (Rotterdam Study), n = 1655 (Leiden Longevity Study), and n = 960 (PROSPER) individuals as indicated. Data are presented as median (center of error bar) and 95% CI (line of error bar) determined by bootstrapping over 1000 iterations.