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Additional file 1 of Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes

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posted on 15.10.2020 by Charles E. Mordaunt, Julia M. Jianu, Benjamin I. Laufer, Yihui Zhu, Hyeyeon Hwang, Keith W. Dunaway, Kelly M. Bakulski, Jason I. Feinberg, Heather E. Volk, Kristen Lyall, Lisa A. Croen, Craig J. Newschaffer, Sally Ozonoff, Irva Hertz-Picciotto, M. Daniele Fallin, Rebecca J. Schmidt, Janine M. LaSalle
Additional file 1: Figure S1. Global CpG methylation is associated with diagnosis and behavioral outcome scores only in males. Figure S2. The proportion of nRBCs is associated with behavioral outcome and global CpG methylation in males. Figure S3. Methylation at ASD DMRs in the discovery set is specifically associated with behavioral outcome. Figure S4. DMRs identified in all discovery subjects distinguish ASD from TD subjects. Figure S5. Sequencing platform has a larger effect on 10 kb window methylation than ASD diagnosis, sex, or study. Figure S6. DMRs identified in males and females distinguish ASD from TD subjects in the replication set. Figure S7. Methylation at ASD DMRs in the replication set is specifically associated with behavioral outcome. Figure S8. DMRs identified in all replication subjects distinguish ASD from TD subjects. Figure S9. The majority of ASD DMRs do not overlap probes on the 450 K and EPIC arrays. Figure S10. DMR methylation assayed by WGBS correlates with DMR methylation assayed by bisulfite pyrosequencing. Figure S11. A subset of ASD diagnosis DMRs are associated with ASD severity in independent sample sets. Figure S12. Machine learning methods workflow. Figure S13. Summary of machine learning datasets and results for males. Figure S14. Summary of machine learning datasets and results for females. Figure S15. ASD DMRs identified with adjustment for sex miss many genes found when stratifying for sex. Figure S16. Replicated ASD DMB genes overlap with replicated ASD DMR genes. Figure S17. ASD DMB genes are enriched for membrane, cell adhesion, and embryo-expressed genes. Figure S18. Neurodevelopmental genes are overrepresented on the X chromosome. Figure S19. Replicated DMR genes on the X chromosome are expressed in fetal brain. Figure S20. Female-specific replicated DMR genes on the X chromosome are expressed in fetal brain. Figure S21. Cord blood ASD DMR genes are significantly enriched for epigenetically dysregulated genes in ASD brain. Figure S22. Selected regions with replicated sex-independent DMR genes on the X chromosome. Figure S23. Selected regions with replicated male-specific DMR genes on the X chromosome. Figure S24. Selected regions with replicated female-specific DMR genes on the X chromosome. Figure S25. ASD DMRs in replication subjects are differentially enriched for chromatin states on the X chromosome. Figure S26. ASD DMRs in discovery subjects are differentially enriched for histone PTMs on the X chromosome. Figure S27. ASD DMRs in replication subjects are differentially enriched for histone PTMs on the X chromosome. Figure S28. ASD DMRs on the X chromosome are enriched near CpG islands only in females.

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National Institute of Environmental Health Sciences National Institute of Child Health and Human Development Environmental Protection Agency (US) Autism Speaks Canadian Institutes of Health

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