Journal article
Cross-Tissue Exploration of Genetic and Epigenetic Effects on Brain Gray Matter in Schizophrenia
Schizophrenia bulletin, Vol.44(2), pp.443-452
02/15/2018
DOI: 10.1093/schbul/sbx068
PMCID: PMC5814943
PMID: 28521044
Abstract
Closely linking genetics and environment factors, epigenetics has been of increasing interest in psychiatric disease studies. In this work, we integrated single nucleotide polymorphisms (SNPs), DNA methylation of blood and saliva, and brain gray matter (GM) measures to explore the role of genetic and epigenetic variation to the brain structure changes in schizophrenia (SZ). By focusing on the reported SZ genetic risk regions, we applied a multi-stage multivariate analysis to a discovery dataset (92 SZ patients and 110 controls, blood) and an independent replication dataset (93 SZ patients and 99 controls, saliva). Two pairs of SNP-methylation components were significantly correlated (r = .48 and .35) in blood DNA, and replicated (r = .46 and .29) in saliva DNA, reflecting cross-tissue SNP cis-effects. In the discovery data, both SNP-related methylation components were also associated with one GM component primarily located in cerebellum, caudate, and thalamus. Additionally, another methylation component in NOSIP gene with significant SZ patient differences (P = .009), was associated with 8 GM components (7 with patient differences) including superior, middle, and inferior frontal gyri, superior, middle, and inferior temporal gyri, cerebellum, insula, cuneus, and lingual gyrus. Of these, 5 methylation-GM associations were replicated (P < .05). In contrast, no pairwise significant associations were observed between SNP and GM components. This study strongly supports that compared to genetic variation, epigenetics show broader and more significant associations with brain structure as well as diagnosis, which can be cross-tissue, and the potential in explaining the mechanism of genetic risks in SZ.
Details
- Title: Subtitle
- Cross-Tissue Exploration of Genetic and Epigenetic Effects on Brain Gray Matter in Schizophrenia
- Creators
- Dongdong Lin - Mind Research NetworkJiayu Chen - Mind Research NetworkStefan Ehrlich - Technische Universität DresdenJuan R Bustillo - University of New MexicoNora Perrone-Bizzozero - University of New MexicoEsther Walton - Georgia State UniversityVincent P Clark - University of New MexicoYu-Ping Wang - Tulane UniversityJing Sui - Chinese Academy of SciencesYuhui Du - Shanxi UniversityBeng C Ho - University of IowaCharles S Schulz - University of MinnesotaVince D Calhoun - University of New MexicoJingyu Liu - University of New Mexico
- Resource Type
- Journal article
- Publication Details
- Schizophrenia bulletin, Vol.44(2), pp.443-452
- DOI
- 10.1093/schbul/sbx068
- PMID
- 28521044
- PMCID
- PMC5814943
- NLM abbreviation
- Schizophr Bull
- ISSN
- 0586-7614
- eISSN
- 1745-1701
- Grant note
- R01 EB006841 / NIBIB NIH HHS P20 GM103472 / NIGMS NIH HHS R01 MH104680 / NIMH NIH HHS R01 MH107354 / NIMH NIH HHS R01 GM109068 / NIGMS NIH HHS R01 EB020407 / NIBIB NIH HHS
- Language
- English
- Date published
- 02/15/2018
- Academic Unit
- Psychiatry
- Record Identifier
- 9984280839402771
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