Widespread methylation quantitative trait loci and their role in schizophrenia risk

Kira A. Perzel Mandell; Nicholas J. Eagles; Richard Wilton; Amanda J. Price; Stephen A. Semick; Leonardo Collado-Torres; Ran Tao; Shizhong Han; Alexander S. Szalay; Thomas M. Hyde; Joel E. Kleinman; Daniel Weinberger; Andrew E. Jaffe

doi:10.1101/2020.09.24.311878

Widespread methylation quantitative trait loci and their role in schizophrenia risk

Kira A. Perzel Mandell, Nicholas J. Eagles, Richard Wilton, Amanda J. Price, Stephen A. Semick, Leonardo Collado-Torres, Ran Tao, Shizhong Han, Alexander S. Szalay, Thomas M. Hyde, Joel E. Kleinman, Daniel Weinberger, Andrew E. Jaffe

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/2020.09.24.311878
State	Published - Sep 24 2020

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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Widespread methylation quantitative trait loci and their role in schizophrenia risk. / Perzel Mandell, Kira A.; Eagles, Nicholas J.; Wilton, Richard; Price, Amanda J.; Semick, Stephen A.; Collado-Torres, Leonardo; Tao, Ran; Han, Shizhong; Szalay, Alexander S.; Hyde, Thomas M.; Kleinman, Joel E.; Weinberger, Daniel ; Jaffe, Andrew E.

In: Unknown Journal, 24.09.2020.

Research output: Contribution to journal › Article › peer-review

Perzel Mandell, Kira A. ; Eagles, Nicholas J. ; Wilton, Richard ; Price, Amanda J. ; Semick, Stephen A. ; Collado-Torres, Leonardo ; Tao, Ran ; Han, Shizhong ; Szalay, Alexander S. ; Hyde, Thomas M. ; Kleinman, Joel E. ; Weinberger, Daniel ; Jaffe, Andrew E. / Widespread methylation quantitative trait loci and their role in schizophrenia risk. In: Unknown Journal. 2020.

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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.",

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AU - Eagles, Nicholas J.

AU - Wilton, Richard

AU - Price, Amanda J.

AU - Semick, Stephen A.

AU - Collado-Torres, Leonardo

AU - Tao, Ran

AU - Han, Shizhong

AU - Szalay, Alexander S.

AU - Hyde, Thomas M.

AU - Kleinman, Joel E.

AU - Weinberger, Daniel

AU - Jaffe, Andrew E.

N1 - Publisher Copyright: The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/9/24

Y1 - 2020/9/24

N2 - 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.

AB - 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.

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