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bioRxiv · 10.1101/2020.09.24.311878

Widespread methylation quantitative trait loci and their role in schizophrenia risk

Perzel Mandell, K. A.·Eagles, N. J.·Wilton, R.·Price, A. J.·Semick, S. A.·Collado-Torres, L.·Tao, R.·Han, S.·Szalay, A. S.·Hyde, T. M.·Kleinman, J. E.·Weinberger, D. R.·Jaffe, A. E.
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Abstract

DNA methylation (DNAm) regulates gene expression and may represent gene-environment interactions. Using whole genome bisulfite sequencing, we surveyed DNAm in a large sample (n=344) of human brain tissues. We identify widespread genetic influence on local methylation levels throughout the genome, with 76% of SNPs and 38% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting putative functional regions that explain much of the heritability associated with risk loci. Furthermore, some CpH sites associated with genetic variation. We have established a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain. One-sentence summaryMost genetic variants associated with DNA methylation levels, and implicated schizophrenia GWAS variants in the human brain.

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Perzel Mandell, K. A., Eagles, N. J., Wilton, R., Price, A. J., Semick, S. A., Collado-Torres, L., Tao, R., Han, S., Szalay, A. S., Hyde, T. M., Kleinman, J. E., Weinberger, D. R., Jaffe, A. E.. 2020-09-24. Widespread methylation quantitative trait loci and their role in schizophrenia risk. https://doi.org/10.1101/2020.09.24.311878

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