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. 2023 Jul 31;15:59. doi: 10.1186/s13073-023-01211-5

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© The Author(s) 2023

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 — Association and validation of immune-cell fractions with sex. a Heatmap of associations between blood cell-type fractions and sex in each of 18 cohorts with sex information. Cohort sizes are shown above heatmap. Red (blue) tones indicate fractions that increase in females (males). P-values derived from a multivariate regression that included age, smoking status, BMI (whenever available), and other study-specific confounders as described in “Methods.” Meta(Stouffer) indicates the directional Stouffer meta-analysis z-statistic and statistical significance. Associations marked with an * are significant after Bonferroni correction at 0.05 level (i.e., P < 0.05/11). b Barplot displaying the effect size estimates and 95% confidence intervals from a fixed effect inverse variance meta-analysis model. Color bar to the right labels the I² values of heteroscedasticity. c Scatterplot of z-statistics from the directional Stouffer method, against the corresponding statistics from the fixed effect meta-analysis model. R-value of agreement is shown. Gray dashed lines indicate the line P = 0.05. d UMAP plots of the scRNA-Seq data of Yazar et al. profiling > 1 million PBMCs from over 900 donors encompassing both sexes as shown. e Scatterplot of Stouffer z-statistics for each cell type derived from DNAm data, against the corresponding t-statistic from Propeller method based on the scRNA-Seq data. Linear regression P-value of agreement is given. f Examples of immune-cell fractions displaying significant associations with sex as inferred from scRNA-Seq data. P-values derive from Propeller