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. 2024 May 17;25:125. doi: 10.1186/s13059-024-03269-9

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© The Author(s) 2024

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Mediating role of LTL. a Mediation analysis of 18 LTL-affecting exposures (y-axis; left) on lifespan (y-axis; right) through LTL with effect size estimates and 95% confidence intervals (CI; x-axis) of the total effect (i.e., IVW MR estimate of exposure on outcome; purple), direct effect (i.e., not mediated by LTL; MVMR estimate; pink) and indirect effect (i.e., LTL mediation by product method; orange) as displayed in the scheme on top of the figure. Displayed are relationships with significant ( $p < 0.05 / 323 = 1.5 e - 4$ ) total and indirect effects. b Schematic illustration of the magnitude and direction of nominally significant MVMR effects ( $p < 0.05$ ; gray arrow). Strictly significant ( $p < 0.05 / 141 = 3.5 e - 4$ ) effects are shown as black arrows. Arrow thickness is proportional to the effect size. Nominally significant effect from lifespan to EA is not displayed. c Mediation analysis of 18 LTL-affecting exposures (y-axis; left) on 17 LTL-affected outcomes (y-axis; right) through LTL. Legend as in a. EA = educational attainment; LDL = low-density lipoprotein; BMI = body mass index; IGF-1 = insulin-like growth factor 1; SHBG = sex hormone binding globulin; LTL = leukocyte telomere length. Labels preceded by an uppercase F denote female-specific traits (i.e., age of first and last live birth)