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Abstract
Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.
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1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
2 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
3 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
4 Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
5 Department of Public Health Sciences, School of Medicine, University of California Davis, Sacramento, CA, USA; MIND Institute, University of California Davis, Sacramento, CA, USA
6 AJ Drexel Autism Institute, Drexel University, Philadelphia, PA, USA; Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA, USA
7 Center for Epigenetics, Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
8 Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
9 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Center for Epigenetics, Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
10 Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Center for Epigenetics, Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA