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Cross-Tissue Exploration of Genetic and Epigenetic Effects on Brain Gray Matter in Schizophrenia
Lin, Dongdong1,2; Chen, Jiayu1,2; Ehrlich, Stefan3; Bustillo, Juan R.4,5; Perrone-Bizzozero, Nora4,5; Walton, Esther6; Clark, Vincent P.1,2,7; Wang, Yu-Ping8; Sui, Jing1,2,9,10; Du, Yuhui1,2,11; Ho, Beng C.12; Schulz, Charles S.13; Calhoun, Vince D.1,2,4,14; Liu, Jingyu1,2,14
AbstractClosely 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.
KeywordBrain Gray Matter Cross-tissue Dna Methylation Genetics Meqtl Schizophrenia
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI ; SSCI
Funding OrganizationNational Institutes of Health(P20GM103472 ; National Science Foundation(1539067) ; R01EB005846)
WOS Research AreaPsychiatry
WOS SubjectPsychiatry
WOS IDWOS:000427534200026
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.Mind Res Network, Albuquerque, NM 87106 USA
2.Lovelace Biomed & Environm Res Inst, Albuquerque, NM 87106 USA
3.Tech Univ Dresden, Div Psychol & Social Med & Dev Neurosci, Fac Med, Dresden, Germany
4.Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA
5.Univ New Mexico, Dept Psychiat, Albuquerque, NM USA
6.Georgia State Univ, Dept Psychol, Univ Plaza, Atlanta, GA 30303 USA
7.Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA
8.Tulane Univ, Dept Biomed Engn, New Orleans, LA 70118 USA
9.Chinese Acad Sci, Inst Automat, Brainnetome Ctr, Beijing, Peoples R China
10.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing, Peoples R China
11.Shanxi Univ, Sch Comp & Informat Technol, Taiyuan, Shanxi, Peoples R China
12.Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA
13.Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA
14.Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA
Recommended Citation
GB/T 7714
Lin, Dongdong,Chen, Jiayu,Ehrlich, Stefan,et al. Cross-Tissue Exploration of Genetic and Epigenetic Effects on Brain Gray Matter in Schizophrenia[J]. SCHIZOPHRENIA BULLETIN,2018,44(2):443-452.
APA Lin, Dongdong.,Chen, Jiayu.,Ehrlich, Stefan.,Bustillo, Juan R..,Perrone-Bizzozero, Nora.,...&Liu, Jingyu.(2018).Cross-Tissue Exploration of Genetic and Epigenetic Effects on Brain Gray Matter in Schizophrenia.SCHIZOPHRENIA BULLETIN,44(2),443-452.
MLA Lin, Dongdong,et al."Cross-Tissue Exploration of Genetic and Epigenetic Effects on Brain Gray Matter in Schizophrenia".SCHIZOPHRENIA BULLETIN 44.2(2018):443-452.
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