Shared Genetic Risk of Schizophrenia and Gray Matter Reduction in 6p22.1

Schizophrenia Bulletin
Jiayu ChenJingyu Liu

Abstract

Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics Consortium (PGC) 108 regions, in 777 discovery samples, we identified 39 SNPs to be significantly associated with SZ-discriminating gray matter volume (GMV) reduction in inferior parietal and superior temporal regions. The findings were replicated in 609 independent samples. These 39 SNPs in chr6:28308034-28684183 (6p22.1), the most significant SZ-risk region reported by PGC, showed regulatory effects on both DNA methylation and gene expression of postmortem brain tissue and saliva. Furthermore, the regulated methylation site and gene showed significantly different levels of methylation and expression in the prefrontal cortex between cases and controls. In addition, for one regulated methylation site we observed a significant in vivo methylation-GMV association in saliva, suggesting a potential SNP-methylation-GMV pathway. Notably, the risk alleles inferred for GMV reduction from in vi...Continue Reading

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Sep 27, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Carol A TammingaRobert Gibbons
Feb 2, 2021·Frontiers in Cellular Neuroscience·Micaël CarrierMichèle Desjardins

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