Dysregulation of DPYSL2 expression by mTOR signaling in schizophrenia: Multi-level study of postmortem brain

Izumi, Ryuta; Hino, Mizuki; Nagaoka, Atsuko; Shishido, Risa; Kakita, Akiyoshi; Hoshino, Mikio; Kunii, Yasuto

doi:10.1016/j.neures.2021.09.004

Cited by 11 publications

(10 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…22 DPYSL2, as another example, has been implicated in multiple neurological disorders and has broad expression in the brain. 23,24…”

Section: Resultsmentioning

confidence: 99%

“…The results show that the proposed pipeline can detect relevant associations as evidenced by the identified SNPs that are located within genes previously linked to neurological disorders such as down syndrome, Alzheimers, schizophrenia, and other neurological disorders. [22][23][24] The inclusion of image-derived phenotypes in our multivariate set-up with canonical component analysis allows for identification of potential biomarkers for diseases like ADHD and how it may affect brain structure. Given these highly correlated traits, multivariate analyses are beneficial to account for these aspects and help to reduce multiple testing problems that are otherwise unavoidable when using a univariate set-up.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A pipeline for multivariate genome-wide associations studies with morphological brain features

Dagasso

Wilms

Forkert

2023

Medical Imaging 2023: Imaging Informatics for Healthcare, Research, and Applications

View full text Add to dashboard Cite

Medical imaging datasets, such as magnetic resonance, are increasingly being used to investigate the genetic architecture of the brain. These images are commonly used as imaging-specific or –derived phenotypes when conducting genotype-phenotype association studies. When using this type of phenotype, multivariate genome-wide association study (GWAS) designs are considered better suited than univariate methods due to the ability to account for the inherent correlations between the phenotypes related to brain structures as determined from medical images. The main objective of this work is to establish and evaluate a comprehensive pipeline for investigating genotype-phenotype associations of the human brain using canonical component analysis. The proposed pipeline was tested to investigate genotype-phenotype associations between cortical brain region volumes in subjects with attention-deficit hyperactivity disorder as a proof-of-principle. Canonical component analysis, a form of multivariate GWAS and machine learning, was utilized to determine genotype-phenotype associations between cortical brain region volumes in subjects with attention-deficit hyperactivity disorder. Using the developed pipeline, several significant (p-value < 5E−04) single nucleotide polymorphisms were found that reside in or near several genes like DSCAM or DPYSL2 that are known to be associated with neurological and mental disorders or substance addiction, a common comorbidity for subjects with attention-deficit hyperactivity disorder. These clinically meaningful results show that the proposed pipeline using canonical component analysis can be used to investigate the genetic architecture of the brain.

show abstract

“…22 DPYSL2, as another example, has been implicated in multiple neurological disorders and has broad expression in the brain. 23,24…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A pipeline for multivariate genome-wide associations studies with morphological brain features

Dagasso

Wilms

Forkert

2023

Medical Imaging 2023: Imaging Informatics for Healthcare, Research, and Applications

View full text Add to dashboard Cite

show abstract

“…DPYSL2, also known as CRMP2, is involved in facilitating neuron guidance, growth and polarity [41][42][43] . It is also implicated in multiple neurological disorders 44 including Alzheimer's disease 45,46 , schizophrenia [47][48][49][50][51][52] , and alcohol-dependence 53 . ITGAE canonically mediates the adhesion of intraepithelial T-lymphocytes to epithelial cells and is involved in intra-tumoral immunity [54][55][56] , but it has also been implicated in Parkinson's disease 57 and Attention-deficit/hyperactivity disorder (ADHD) [58][59][60] .…”

Section: Discussionmentioning

confidence: 99%

Disentangling the roles of trauma and genetics in psychiatric disorders using an Electronic Health Records-based approach

Marchese

Cuddleston

Seah

et al. 2022

Preprint

View full text Add to dashboard Cite

Posttraumatic stress disorder (PTSD) requires an exposure to trauma for diagnosis by the DSM-V. Despite this, there is no documented linear relationship between degree of trauma and severity/chronicity of PTSD.To determine whether traumatic and stressful life events (TSLEs) collected from Electronic Health Records (EHR) interact with PTSD genetics to better define individual risk of developing PTSD. We collected trauma information from patient records in the Mount Sinai BioMe™ biobank population-based cohort and tested for associations with PTSD. We generated a TSLE risk score (TRS), tested its association with PTSD, and for interactions with a polygenic risk score (PRS) of PTSD and a GWAS of PTSD using our biobank population.We used the Mount Sinai BioMe™ biobank patient population of 31,704 individuals with matched genotype and EHR data, which has been enrolling patients since 2006. Patient enrollment in BioMe™ is unrestricted, resulting in high diversity. Our study includes 1,990 individuals with PTSD and 28,478 individuals without PTSD from the Mount Sinai BioMe™ biobank.A total of 1,990 individuals with PTSD and 28,478 controls were analyzed (average age 42-78 years, 58.7% women). We identified a total of 22 EHR-derived TSLEs that were associated with PTSD (β> 0.029, p<1.61×10−3). TSLEs interacted with each other to increase the risk of developing PTSD, with the most significant interaction between being female (as a proxy for experiencing sexism) and being HIV+ (β=0.013, p=8.9×10−11). PRS of PTSD and lead SNPS from GWAS interacted with TSLEs and our TRS to increase PTSD risk. In addition to TRS interactions, we found significant interactions between PTSD PRS and domestic violence, and sexual assault in European Americans (β>207.74, p<1.80×10−3). rs113282988 and rs189796944 variants reached genome-wide significance in interactions with TRS (β>0.056, p<9.04×10−9), and rs189796944 in an interaction with Physical Survival TSLEs (β>0.127, p<4×10−8).In conclusion, quantification of trauma type, severity, and magnitude—alone and in concert with genetics—provides better prediction of PTSD risk than PRS alone. Understanding who is at risk of developing PTSD allows for timely clinical intervention and possible prevention.

show abstract

“…We have used postmortem brains without a history of psychiatric diseases from the Brain Research Institute, Niigata University, as controls in our previous studies. [17][18][19][20] This study was approved by the Ethics Committee of Fukushima 21 For each patient with schizophrenia, the daily dosage of antipsychotics within 3 months before death was indicated as the chlorpromazine equivalent dose (CPeq) (mg/day).…”

Section: Quantifiable Differencesmentioning

confidence: 99%

Availability of individual proteins for quantitative analysis in postmortem brains preserved in two different brain banks

Nagaoka,

Hino,

Izumi

et al. 2024

Neuropsychopharm Rep

Self Cite

View full text Add to dashboard Cite

AimPostmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities.MethodsWe compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain.ResultsWe found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions.ConclusionsWhen studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions.

show abstract

Dysregulation of DPYSL2 expression by mTOR signaling in schizophrenia: Multi-level study of postmortem brain

Cited by 11 publications

References 31 publications

A pipeline for multivariate genome-wide associations studies with morphological brain features

A pipeline for multivariate genome-wide associations studies with morphological brain features

Disentangling the roles of trauma and genetics in psychiatric disorders using an Electronic Health Records-based approach

Availability of individual proteins for quantitative analysis in postmortem brains preserved in two different brain banks

Contact Info

Product

Resources

About