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. 2022 Nov 21;54(12):1786–1794. doi: 10.1038/s41588-022-01208-7

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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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Extended Data Fig. 3 — P value inflation in Stage-2 analysis: Quantile-quantile plot for Stage-2 (without exome-extract samples), based on a ordinal logistic burden test (see Methods). Results are shown for all burden tests (n = 20,681) for which at least 10 damaging alleles were present in this dataset (based on 4 different variant deleteriousness thresholds per gene). While not used in this analysis, the threshold for multiple testing correction based on FDR < 0.1 is shown for reference. The genomic p-value inflation was 1.016. Note that causative mutations were not separately removed in Stage-2, as we focused on a specific set of genes.