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. 2022 Jul 1;13:3790. doi: 10.1038/s41467-022-30805-7

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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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Fig. 6 — a Bar plots for the family-adjusted prevalence of predicted pathogenic (PP) heteroplasmies and heteroplasmies at nonsynonymous sites in oxidative phosphorylation genes or at all sites in tRNA genes (OXPHOS/tRNA), respectively. Error bars represent bootstrapped SEM. Two-sided P values are from logistic regression further adjusted for mtDNA content z-score. b Forest plots for the effects of per standard deviation increase in pathogenicity z-score on transmission of maternal mtDNA heteroplasmies to the child. Horizontal black lines represent the 95% confidence interval of the odds ratio (OR) among children indicated by the label on the y axis (from top to bottom, BBC: n = 376, 82, 221, and 318 children; SSC: n = 1938 siblings and 1938 probands; Meta: n = 2314, 2020, and 539 children). Combined effects were estimated based on a fixed-effect meta-analysis (Meta) of the results from the SSC and BBC. Values on the x axis are shown on a logarithmic scale. c Box plots for the distribution of pathogenicity z-scores among de novo heteroplasmies (from left to right, NT: n = 24, 30; NDD: n = 52, 50) in children born to mothers aged below and above 30 years. Two-sided P values are from linear regression. All box-plot elements are defined in the same way as in Fig. 1. d Maternal age-dependent increase in the number of de novo heteroplasmies. Points and error bars represent mean ± SEM among children (from left to right, NT: n = 242, 134; NDD: n = 368, 253) in the two maternal-age groups in (c). The P value (two-sided) and the shaded area indicate the significance of the slope and the 95% confidence interval of the linear regression line (the solid line), respectively. ASD: autism spectrum disorder; ADHD: attention-deficit/hyperactivity disorder; DD: developmental delay; NDD: neurodevelopmental disorder.