Exploring different impaired speed of genetic-related brain function and structures in schizophrenic progress using multimodal analysis*

Published on Jul 1, 2018 in EMBC (International Conference of the IEEE Engineering in Medicine and Biology Society)
· DOI :10.1109/embc.2018.8513313
Na Luo2
Estimated H-index: 2
(CAS: Chinese Academy of Sciences),
Lin Tian8
Estimated H-index: 8
+ 6 AuthorsJing Sui31
Estimated H-index: 31
(CAS: Chinese Academy of Sciences)
Schizophrenia (SZ) is a highly heritable disease exhibiting substantial structural and functional brain impairments. The duration of illness and medication use may cause different presentations of impairments in patients. To understand the progressive variations of the disease, most recent studies have reported brain functional or structural abnormalities associated with illness duration, but a comprehensive study of pathology underlying brain structure, function and illness duration is still limited. In this work, we employed a three-way parallel independent component analysis (pICA) algorithm to jointly analyze grey matter volume(GM), functional connectivity (FC) and single nucleotide polymorphisms (SNPs) from drug-naive first-episode [FESZ], chronic schizophrenia [CSZ]) and healthy controls[HC], aiming to identify the linked alterations in SNP-GM-FC components, and evaluate the impairment speed of imaging measures associated with SZ-susceptible genetic variants in different disease stages (FESZ and CSZ). Results demonstrated significant group differences on GM and FC in hippocampus, temporal gyrus and cerebellum between SZ and HC, which are also significantly correlated with SNPs residing in genes like GABBR2, SATB2, CACNA1C, PDE4B, involved in pathways of cell junction, synapse and neuron projection. Moreover, two-sample t-tests showed that GM volume and FC strength presented similar trends of progressive decrease with the increase of the illness duration (HC>FESZ>CSZ). Besides that genetic-related GM and FC components both showed significant associations with illness duration, FC indicates the higher impairment speed than GM, suggesting that functional connectivity may serve as a more sensitive measure to detect the disruptions in SZ at the very early stage.
  • References (16)
  • Citations (1)
📖 Papers frequently viewed together
12 Citations
50 Citations
35 Authors (Na Luo, ..., Tianzi Jiang)
3 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Dongdong Lin (The Mind Research Network)H-Index: 13
#2Jiayu Chen (The Mind Research Network)H-Index: 16
Last. Jingyu Liu (UNM: University of New Mexico)H-Index: 30
view all 14 authors...
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 ...
14 CitationsSource
#1Tao Li (Sichuan University)H-Index: 46
#2Qiang Wang (Sichuan University)H-Index: 27
Last. Jianfeng FengH-Index: 37
view all 22 authors...
Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naive), and chronic pat...
57 CitationsSource
#1Godfrey D. Pearlson (Yale University)H-Index: 110
#2Jingyu Liu (UNM: University of New Mexico)H-Index: 30
Last. Vince D. Calhoun (Yale University)H-Index: 93
view all 3 authors...
Complex inherited phenotypes, including those for many common medical and psychiatric diseases, are most likely underpinned by multiple genes contributing to interlocking molecular biological processes, along with environmental factors (Owen et al., 2010). Despite this, genotyping strategies for complex, inherited, disease-related phenotypes mostly employ univariate analyses, e.g. genome wide association (GWA). Such procedures most often identify isolated risk-related SNPs or loci, not the under...
39 CitationsSource
#1Victor M. Vergara (The Mind Research Network)H-Index: 10
#2Alvaro Ulloa (UNM: University of New Mexico)H-Index: 6
Last. Jingyu Liu (UNM: University of New Mexico)H-Index: 30
view all 6 authors...
Multi-modal data analysis techniques, such as the Parallel Independent Component Analysis (pICA), are essential in neuroscience, medical imaging and genetic studies. The pICA algorithm allows the simultaneous decomposition of up to two data modalities achieving better performance than separate ICA decompositions and enabling the discovery of links between modalities. However, advances in data acquisition techniques facilitate the collection of more than two data modalities from each subject. Exa...
26 CitationsSource
#1Stephan Ripke (Broad Institute)H-Index: 74
#2Benjamin M. Neale (Broad Institute)H-Index: 85
Last. Michael O. Donovan (Cardiff University)H-Index: 122
view all 300 authors...
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations wer...
3,480 CitationsSource
#1Jing Wang (Vandy: Vanderbilt University)H-Index: 34
#2Dexter T. Duncan (Vandy: Vanderbilt University)H-Index: 7
Last. Bing Zhang (Vandy: Vanderbilt University)H-Index: 40
view all 4 authors...
Functional enrichment analysis is an essential task for the interpretation of gene lists derived from large-scale genetic, transcriptomic and proteomic studies. WebGestalt (WEB-based GEne SeT AnaLysis Toolkit) has become one of the popular software tools in this field since its publication in 2005. For the last 7 years, WebGestalt data holdings have grown substantially to satisfy the requirements of users from different research areas. The current version of WebGestalt supports 8 organisms and 2...
945 CitationsSource
#1Jiayu Chen (UNM: University of New Mexico)H-Index: 16
#2Vince D. CalhounH-Index: 93
Last. Jingyu Liu (UNM: University of New Mexico)H-Index: 30
view all 9 authors...
Abstract Recently, deriving candidate endophenotypes from brain imaging data has become a valuable approach to study genetic influences on schizophrenia (SZ), whose pathophysiology remains unclear. In this work we utilized a multivariate approach, parallel independent component analysis, to identify genomic risk components associated with brain function abnormalities in SZ. 5157 candidate single nucleotide polymorphisms (SNPs) were derived from genome-wide array based on their possible connectio...
40 CitationsSource
#1Carl A. Anderson (Wellcome Trust Centre for Human Genetics)H-Index: 39
#2Fredrik Pettersson (Wellcome Trust Centre for Human Genetics)H-Index: 13
Last. Krina T. Zondervan (Wellcome Trust Centre for Human Genetics)H-Index: 53
view all 6 authors...
This protocol details the data quality assessment and control steps that are typically carried out during case-control association studies. The steps described involve the identification and removal of DNA samples and markers that introduce bias to the study. These critical steps are paramount to the success of a case-control study and are necessary before statistically testing for association. We describe how to use PLINK, a tool for handling SNP data, to carry out assessments of failure rate p...
477 CitationsSource
#1Shaun Purcell (MIT: Massachusetts Institute of Technology)H-Index: 102
#2Benjamin M. Neale (MIT: Massachusetts Institute of Technology)H-Index: 85
Last. Pak C. Sham (HKU: University of Hong Kong)H-Index: 106
view all 11 authors...
Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can ...
15.3k CitationsSource
#1Hilleke E. Hulshoff Pol (UU: Utrecht University)H-Index: 73
#2René S. Kahn (UU: Utrecht University)H-Index: 108
Numerous imaging studies have revealed structural brain changes in schizophrenia. Decreases in brain tissue are accompanied by increases in ventricle volumes and cerebrospinal fluid. Whether or not these brain changes are progressive beyond the first episode is subject to debate. To assess if progressive brain changes occur in chronically ill patients, 11 longitudinal magnetic resonance imaging and computed tomography studies were reviewed. Patients were ill for on average 10 years at their init...
274 CitationsSource
Cited By1
#1Lifei Wang (PRC: China Medical University (PRC))
#2Yimeng Zhao (PRC: China Medical University (PRC))
Last. Shengnan Wei (PRC: China Medical University (PRC))H-Index: 8
view all 12 authors...
Finding neural features of suicide attempts (SA) in major depressive disorder (MDD) may be helpful in preventing suicidal behavior. The ventral and medial prefrontal cortex (PFC), as well as the amygdala form a circuit implicated in emotion regulation and the pathogenesis of MDD. The aim of this study was to identify whether patients with MDD who had a history of SA show structural and functional connectivity abnormalities in the amygdala and PFC relative to MDD patients without a history of SA....
#1Na Luo (CAS: Chinese Academy of Sciences)H-Index: 2
#2Lin TianH-Index: 8
Last. Jing Sui (CAS: Chinese Academy of Sciences)H-Index: 31
view all 13 authors...
Abstract The progress of schizophrenia at various stages is an intriguing question, which has been explored to some degree using single-modality brain imaging data, e.g. gray matter (GM) or functional connectivity (FC). However it remains unclear how those changes from different modalities are correlated with each other and if the sensitivity to duration of illness and disease stages across modalities is different. In this work, we jointly analyzed FC, GM volume and single nucleotide polymorphis...