TY - JOUR
T1 - Genome-wide sequencing-based identification of methylation quantitative trait loci and their role in schizophrenia risk
AU - Perzel Mandell, Kira A.
AU - Eagles, Nicholas J.
AU - Wilton, Richard
AU - Price, Amanda J.
AU - Semick, Stephen A.
AU - Collado-Torres, Leonardo
AU - Ulrich, William S.
AU - Tao, Ran
AU - Han, Shizhong
AU - Szalay, Alexander S.
AU - Hyde, Thomas M.
AU - Kleinman, Joel E.
AU - Weinberger, Daniel R.
AU - Jaffe, Andrew E.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - DNA methylation (DNAm) is an epigenetic regulator of gene expression and a hallmark of gene-environment interaction. Using whole-genome bisulfite sequencing, we have surveyed DNAm in 344 samples of human postmortem brain tissue from neurotypical subjects and individuals with schizophrenia. We identify genetic influence on local methylation levels throughout the genome, both at CpG sites and CpH sites, with 86% of SNPs and 55% 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 the genes and regions with which these loci are epigenetically associated. These findings can be used to better characterize schizophrenia GWAS-identified variants as epigenetic risk variants. Regions differentially methylated by schizophrenia risk-SNPs explain much of the heritability associated with risk loci, despite covering only a fraction of the genomic space. We provide 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) is an epigenetic regulator of gene expression and a hallmark of gene-environment interaction. Using whole-genome bisulfite sequencing, we have surveyed DNAm in 344 samples of human postmortem brain tissue from neurotypical subjects and individuals with schizophrenia. We identify genetic influence on local methylation levels throughout the genome, both at CpG sites and CpH sites, with 86% of SNPs and 55% 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 the genes and regions with which these loci are epigenetically associated. These findings can be used to better characterize schizophrenia GWAS-identified variants as epigenetic risk variants. Regions differentially methylated by schizophrenia risk-SNPs explain much of the heritability associated with risk loci, despite covering only a fraction of the genomic space. We provide 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.
UR - http://www.scopus.com/inward/record.url?scp=85114647313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114647313&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-25517-3
DO - 10.1038/s41467-021-25517-3
M3 - Article
C2 - 34475392
AN - SCOPUS:85114647313
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5251
ER -