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 vivo imaging are all consistent with the risk alleles for SZ inferred from postmortem data. Collectively, we provide evidence for shared genetic risk of SZ and regional GMV reduction in 6p22.1 and demonstrate potential molecular mechanisms that may drive the observed in vivo associations. This study motivates dissecting SZ-risk variants to better understand their associations with focal brain phenotypes and the complex pathophysiology of the illness.
journal_name
Schizophr Bulljournal_title
Schizophrenia bulletinauthors
Chen J,Calhoun VD,Lin D,Perrone-Bizzozero NI,Bustillo JR,Pearlson GD,Potkin SG,van Erp TGM,Macciardi F,Ehrlich S,Ho BC,Sponheim SR,Wang L,Stephen JM,Mayer AR,Hanlon FM,Jung RE,Clementz BA,Keshavan MS,Gershon ES,Swdoi
10.1093/schbul/sby010subject
Has Abstractpub_date
2019-01-01 00:00:00pages
222-232issue
1eissn
0586-7614issn
1745-1701pii
4885372journal_volume
45pub_type
杂志文章abstract::There is an increasing emphasis on identifying individuals with schizophrenia earlier and earlier in their disease process, with the assumption that earlier identification translates into earlier treatment, which translates into improved outcome. Unfortunately, one age cohort, children under 13 years of age, have been...
journal_title:Schizophrenia bulletin
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1093/schbul/sbq018
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journal_title:Schizophrenia bulletin
pub_type: 评论,杂志文章
doi:10.1093/schbul/sbu139
更新日期:2015-01-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbi014
更新日期:2005-07-01 00:00:00
abstract::In subjects at risk for psychosis, the studies on gray matter volume (GMV) predominantly reported volume loss compared with healthy controls (CON). However, other important morphological measurements such as cortical surface area (CSA) and cortical thickness (CT) were not systematically compared. So far, samples mostl...
journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbaa066
更新日期:2020-12-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,评审
doi:10.1093/schbul/sbm016
更新日期:2007-07-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbz051
更新日期:2020-02-26 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbs148
更新日期:2013-11-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,评审
doi:10.1093/schbul/sbn059
更新日期:2008-09-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/oxfordjournals.schbul.a006860
更新日期:2001-01-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/oxfordjournals.schbul.a007144
更新日期:2004-01-01 00:00:00
abstract::The study describes the Cardiff Anomalous Perceptions Scale (CAPS), a new validated measure of perceptual anomalies. The 32-item CAPS measure is a reliable, self-report scale, which uses neutral language, demonstrates high content validity, and includes subscales that measure distress, intrusiveness, and frequency of ...
journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbj014
更新日期:2006-04-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbt153
更新日期:2014-09-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,meta分析,评审
doi:10.1093/schbul/sbs060
更新日期:2013-07-01 00:00:00
abstract::Approximately 100 years ago, a prominent German public figure name Daniel Schreber wrote memoirs of his experiences in asylums. His case was diagnosed Dementia Praecox at times and Paranoia at others by his treaters. Freud analyzed Schreber's memoirs from the perspective of his "libido" theory of developmentally organ...
journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbp019
更新日期:2009-05-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,评审
doi:10.1093/schbul/sbv035
更新日期:2015-11-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,评审
doi:10.1093/oxfordjournals.schbul.a033333
更新日期:1998-01-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,评审
doi:10.1093/schbul/sbv071
更新日期:2015-09-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbr058
更新日期:2013-01-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbu150
更新日期:2015-01-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbq028
更新日期:2010-05-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,评审
doi:10.1093/schbul/sbx089
更新日期:2017-09-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbp124
更新日期:2010-05-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sbaa157
更新日期:2020-10-24 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,评审
doi:10.1093/schbul/sbm056
更新日期:2007-07-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章,meta分析,评审
doi:10.1093/schbul/sbx088
更新日期:2018-04-06 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/6.2.275
更新日期:1980-01-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/oxfordjournals.schbul.a006946
更新日期:2002-01-01 00:00:00
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journal_title:Schizophrenia bulletin
pub_type: 杂志文章
doi:10.1093/schbul/sby113
更新日期:2019-06-18 00:00:00