Associations between polygenic risk scores and amplitude of low-frequency fluctuation of inferior frontal gyrus in schizophrenia

2022 ◽  
Author(s):  
Jujiao Kang ◽  
Zeyu Jiao ◽  
Yue Qin ◽  
Yi Wang ◽  
Jiucun Wang ◽  
...  
Keyword(s):  
Inferior Frontal Gyrus ◽  
Low Frequency ◽  
Frequency Fluctuation ◽  
Risk Scores ◽  
Polygenic Risk

scholarly journals Polygenic Risk Scores Augment Stroke Subtyping

2021 ◽  
Vol 7 (2) ◽  
pp. e560
Author(s):  
Jiang Li ◽  
Durgesh P. Chaudhary ◽  
Ayesha Khan ◽  
Christoph Griessenauer ◽  
David J. Carey ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Genetic Correlation ◽  
Genome Wide Association Study ◽  
Low Frequency ◽  
European Ancestry ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Large Artery ◽  
Polygenic Risk ◽  
Gene Sets

ObjectiveTo determine whether the polygenic risk score (PRS) derived from MEGASTROKE is associated with ischemic stroke (IS) and its subtypes in an independent tertiary health care system and to identify the PRS derived from gene sets of known biological pathways associated with IS.MethodsControls (n = 19,806/7,484, age ≥69/79 years) and cases (n = 1,184/951 for discovery/replication) of acute IS with European ancestry and clinical risk factors were identified by leveraging the Geisinger Electronic Health Record and chart review confirmation. All Geisinger MyCode patients with age ≥69/79 years and without any stroke-related diagnostic codes were included as low risk control. Genetic heritability and genetic correlation between Geisinger and MEGASTROKE (EUR) were calculated using the summary statistics of the genome-wide association study by linkage disequilibrium score regression. All PRS for any stroke (AS), any ischemic stroke (AIS), large artery stroke (LAS), cardioembolic stroke (CES), and small vessel stroke (SVS) were constructed by PRSice-2.ResultsA moderate heritability (10%–20%) for Geisinger sample as well as the genetic correlation between MEGASTROKE and the Geisinger cohort was identified. Variation of all 5 PRS significantly explained some of the phenotypic variations of Geisinger IS, and the R2 increased by raising the cutoff for the age of controls. PRSLAS, PRSCES, and PRSSVS derived from low-frequency common variants provided the best fit for modeling (R2 = 0.015 for PRSLAS). Gene sets analyses highlighted the association of PRS with Gene Ontology terms (vascular endothelial growth factor, amyloid precursor protein, and atherosclerosis). The PRSLAS, PRSCES, and PRSSVS explained the most variance of the corresponding subtypes of Geisinger IS suggesting shared etiologies and corroborated Geisinger TOAST subtyping.ConclusionsWe provide the first evidence that PRSs derived from MEGASTROKE have value in identifying shared etiologies and determining stroke subtypes.

scholarly journals Altered patterns of fractional amplitude of low-frequency fluctuation and regional homogeneity in abstinent methamphetamine-dependent users

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
An Xie ◽  
Qiuxia Wu ◽  
Winson Fu Zun Yang ◽  
Chang Qi ◽  
Yanhui Liao ◽  
...  
Keyword(s):  
Resting State ◽  
Brain Activity ◽  
Inferior Frontal Gyrus ◽  
Low Frequency ◽  
Regional Homogeneity ◽  
Anterior Cingulate ◽  
Frequency Fluctuation ◽  
Early Recovery ◽  
Left Inferior Frontal Gyrus ◽  
The Right

AbstractMethamphetamine (MA) could induce functional and structural brain alterations in dependent subjects. However, few studies have investigated resting-state activity in methamphetamine-dependent subjects (MADs). We aimed to investigate alterations of brain activity during resting-state in MADs using fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). We analyzed fALFF and ReHo between MADs (n = 70) and healthy controls (HCs) (n = 84) and performed regression analysis using MA use variables. Compared to HCs, abstinent MADs showed increased fALFF and ReHo values in the bilateral striatum, decreased fALFF in the left inferior frontal gyrus, and decreased ReHo in the bilateral anterior cingulate cortex, sensorimotor cortex, and left precuneus. We also observed the fALFF values of bilateral striatum were positively correlated with the age of first MA use, and negatively correlated with the duration of MA use. The fALFF value of right striatum was also positively correlated with the duration of abstinence. The alterations of spontaneous cerebral activity in abstinent MADs may help us probe into the neurological pathophysiology underlying MA-related dysfunction and recovery. Since MADs with higher fALFF in the right striatum had shorter MA use and longer abstinence, the increased fALFF in the right striatum might implicate early recovery during abstinence.

scholarly journals Stress Mediating Genes in Aging, Health, and Longevity Traits: Effects of Multiple Interactions

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 286-286
Author(s):  
Anatoliy Yashin ◽  
Dequing Wu ◽  
Konstantin Arbeev ◽  
Arseniy Yashkin ◽  
Galina Gorbunova ◽  
...  
Keyword(s):  
Strong Interaction ◽  
Genetic Interaction ◽  
Interaction Effects ◽  
Genetic Interactions ◽  
Risk Scores ◽  
Data Sets ◽  
Interaction Patterns ◽  
Polygenic Risk ◽  
Drug Candidates ◽  
Aging Health

Abstract Persistent stress of external or internal origin accelerates aging, increases risk of aging related health disorders, and shortens lifespan. Stressors activate stress response genes, and their products collectively influence traits. The variability of stressors and responses to them contribute to trait heterogeneity, which may cause the failure of clinical trials for drug candidates. The objectives of this paper are: to address the heterogeneity issue; to evaluate collective interaction effects of genetic factors on Alzheimer’s disease (AD) and longevity using HRS data; to identify differences and similarities in patterns of genetic interactions within two genders; and to compare AD related genetic interaction patterns in HRS and LOADFS data. To reach these objectives we: selected candidate genes from stress related pathways affecting AD/longevity; implemented logistic regression model with interaction term to evaluate effects of SNP-pairs on these traits for males and females; constructed the novel interaction polygenic risk scores for SNPs, which showed strong interaction potential, and evaluated effects of these scores on AD/longevity; and compared patterns of genetic interactions within the two genders and within two datasets. We found there were many genes involved in highly significant interactions that were the same and that were different within the two genders. The effects of interaction polygenic risk scores on AD were strong and highly statistically significant. These conclusions were confirmed in analyses of interaction effects on longevity trait using HRS data. Comparison of HRS to LOADFS data showed that many genes had strong interaction effects on AD in both data sets.

scholarly journals Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance‐Naïve Children: Results from the ABCD Study

2021 ◽  
Author(s):  
Alexander S. Hatoum ◽  
Emma C. Johnson ◽  
David A. A. Baranger ◽  
Sarah E. Paul ◽  
Arpana Agrawal ◽  
...  
Keyword(s):  
Brain Structure ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Alcohol Involvement
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