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. 2021 Aug 26;12:5134. doi: 10.1038/s41467-021-25474-x

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© The Author(s) 2021

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. 1 — DNA methylation was fine-mapped at 521 genes in the ALP in the appendix of PD patients and controls (n = 24 and 19 individuals, respectively). a Manhattan plot demonstrating differential methylation in PD appendix. There were 326 genes in the ALP exhibiting differential methylation in PD relative to controls (928 cytosine sites at q < 0.05, robust linear regression). Highlighted are genes implicated in both our study and PD GWAS²³. Signed log p refers to the significance of differentially methylated cytosines, with sign corresponding to the direction of DNA methylation change (hypermethylation, green or hypomethylated, blue). b Fraction of significantly hypomethylated (blue) and hypermethylated (green) sites in the PD appendix, as compared to all sites (gray). P-value represents two-sided Fisher’s exact test for enrichment of hypermethylated sites among significant versus non-significant cytosines. c Genomic elements enriched with significant differentially methylated sites in the PD appendix. Filled circles represent *p < 0.05, **p < 0.01, and ***p < 0.001, two-sided Fisher’s exact test on n = 182,024 cytosines comparing the odds of observing significant cytosines within versus outside of the genomic element. Error bars indicate 95% confidence intervals. d ALP pathways enriched with differential methylation and differential gene expression. Filled bars represent *p < 0.05 and ***p < 0.001, two-sided Fisher’s exact test comparing the odds of observing significant cytosines at genes belonging to the selected pathway versus the other targeted ALP genes. e Pathways affected by transcriptomic changes in the PD appendix. Pathways for the differentially expressed genes in the PD appendix were obtained using DAVID and visualized with EnrichmentMap and AutoAnnotate in Cytoscape (v3.7.1). Node colors represent normalized enrichment score, where darker red signifies greater enrichment. Actual p values are reported in Supplementary Data 21.