scholarly journals Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
L. M. Reus ◽  
X. Shen ◽  
J. Gibson ◽  
E. Wigmore ◽  
L. Ligthart ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Illness ◽  
White Matter Integrity ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Subcortical Volumes

scholarly journals Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

2016 ◽  
Author(s):  
LM Reus ◽  
X Shen ◽  
J Gibson ◽  
E Wigmore ◽  
L Ligthart ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Regions ◽  
Uk Biobank ◽  
Imaging Data ◽  
Brain Volumes ◽  
Polygenic Risk ◽  
Subcortical Brain ◽  
The Impact ◽  
Subcortical Volumes

AbstractMajor depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data compromised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). Our, findings however, indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. In the current study, we found little or no evidence for genetic overlap between major psychiatric disorders and structural brain measures. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.

scholarly journals Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank

2020 ◽  
Author(s):  
Xingxing Zhu ◽  
Joey Ward ◽  
Breda Cullen ◽  
Donald M. Lyall ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Cortical Thickness ◽  
Brain Structure ◽  
Anterior Cingulate ◽  
White Matter Integrity ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Matter Volume

AbstractBackgroundAnhedonia is a core symptom of multiple psychiatric disorders and has been associated with changes in brain structure. Genome-wide association studies suggest that anhedonia is heritable with a polygenic architecture but few studies have explored the association between genetic loading for anhedonia - indexed by polygenic risk scores for anhedonia (PRS-anhedonia) - and structural brain imaging phenotypes. We investigated how anhedonia and polygenic risk for anhedonia were associated with brain structure within the UK Biobank cohort.MethodsBrain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness and white matter integrity) were analysed in relation to the self-reported anhedonia phenotype and PRS-anhedonia for 17,492 participants (8,506 males and 8,986 females; mean age = 62.81 years, SD = 7.43), using linear mixed models and including mediation analyses.ResultsState anhedonia was significantly associated with smaller total grey matter volume (GMV), smaller volumes in thalamus and nucleus accumbens; as well as reduced cortical thickness within the paracentral gyrus, the opercular part of inferior frontal gyrus and the rostral anterior cingulate cortex. PRS-anhedonia was associated with reduced total GMV, increased total white matter volume and reduced white matter integrity; in addition to reduced cortical thickness within the parahippocampal cortex, the superior temporal gyrus and the insula cortex.ConclusionsBoth the state anhedonia phenotype and PRS-anhedonia were associated with differences in multiple brain structures/areas, including within reward-related circuits. These differences may represent vulnerability markers for psychopathology across a range of psychiatric disorders.

scholarly journals Polygenic Risk and White Matter Integrity in Individuals at High Risk of Mood Disorder

2013 ◽  
Vol 74 (4) ◽  
pp. 280-286 ◽  
Author(s):  
Heather C. Whalley ◽  
Emma Sprooten ◽  
Suzanna Hackett ◽  
Lynsey Hall ◽  
Douglas H. Blackwood ◽  
...  
Keyword(s):  
White Matter ◽  
High Risk ◽  
Mood Disorder ◽  
White Matter Integrity ◽  
Polygenic Risk

Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia

2022 ◽  
pp. 1-10
Author(s):  
Wenjun Su ◽  
Aihua Yuan ◽  
Yingying Tang ◽  
Lihua Xu ◽  
Yanyan Wei ◽  
...  
Keyword(s):  
White Matter ◽  
Functional Connectivity ◽  
White Matter Integrity ◽  
First Episode ◽  
Polygenic Risk Score ◽  
Polygenic Inheritance ◽  
Polygenic Risk ◽  
Corona Radiata ◽  
Brain White Matter ◽  
First Episode Schizophrenia

Abstract Background Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. Methods Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. Results Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)–left inferior temporal gyrus (ITG), right IFG–left ITG, right IFG–left middle frontal gyrus (MFG), and right IFG–right MFG in the FES group. Conclusion Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

scholarly journals Do Cerebral Small Vessel Disease and Multiple Sclerosis Share Common Mechanisms of White Matter Injury?

Stroke ◽  
2019 ◽  
Vol 50 (8) ◽  
pp. 1968-1972 ◽  
Author(s):  
Robin B. Brown ◽  
Matthew Traylor ◽  
Stephen Burgess ◽  
Stephen Sawcer ◽  
Hugh S. Markus
Keyword(s):  
Multiple Sclerosis ◽  
Relative Risk ◽  
White Matter ◽  
Risk Score ◽  
White Matter Injury ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Uk Biobank ◽  
Single Nucleotide ◽  
Polygenic Risk

Background and Purpose— The role of inflammation in ischemic white matter disease is increasingly recognized, and further understanding of the pathophysiology might inform future treatment strategies. Multiple sclerosis (MS) is a chronic autoimmune condition in which inflammation plays a central role that also affects the white matter. We hypothesized that white matter injury might share common mechanisms and used statistical genetics techniques to assess whether having genetically elevated white matter hyperintensity (WMH) volume was associated with increased MS risk. Methods— We investigated the genetic association in 2 cohorts with magnetic resonance imaging-quantified ischemic white matter lesion volume (WMH in stroke; n=2797 and UK Biobank; n=8353) and 14 802 cases of MS and 26 703 controls from the International Multiple Sclerosis Genetics Consortium. We further performed individual-level polygenic risk score calculations for MS and measures of structural white matter disease in UK Biobank. Finally, we looked for evidence of overlapping risk across the whole genome. Results— There was no association of genetic variants influencing MS with WMH volume using summary statistics in the WMH in stroke cohort (relative risk score =1.014; 95% CI, 0.936–1.110) or in the UK Biobank cohort (relative risk score =1.030; 95% CI, 0.932–1.117). Conversely, assessing the contribution of single nucleotide polymorphisms significantly associated with WMH on the risk of MS there was no significant association (relative risk score =0.930; 95% CI, 0.736–1.191). There were no significant associations between polygenic risk scores calculations; these results were robust to the selection of single nucleotide polymorphisms at a range of significance thresholds. Whole genome analysis did not reveal any overlap of risk between the traits. Conclusions— Our results do not provide evidence to suggest a shared mechanism of white matter damage in ischemia and MS. We propose that inflammation acts in distinct pathways because of the differing nature of the primary insult.

scholarly journals Association of whole-genome and NETRIN1 signaling pathway-derived polygenic risk scores for Major Depressive Disorder and thalamic radiation white matter microstructure in UK Biobank

2018 ◽  
Author(s):  
Miruna C. Barbu ◽  
Yanni Zeng ◽  
Xueyi Shen ◽  
Simon R. Cox ◽  
Toni-Kim Clarke ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
White Matter ◽  
Depressive Disorder ◽  
Signaling Pathway ◽  
Risk Scores ◽  
Whole Genome ◽  
Uk Biobank ◽  
Major Depressive ◽  
Polygenic Risk ◽  
White Matter Microstructure

AbstractBackgroundMajor Depressive Disorder (MDD) is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome, and growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide an important route for identification of disease mechanisms by focusing on a specific process excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether MDD polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRS) and the whole genome excluding NETRIN1 pathway genes (genomic-PRS) were associated with white matter integrity.MethodsWe used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: N = 6,401; MD: N = 6,390).ResultsWe found significantly lower FA in the superior longitudinal fasciculus (β = -0.035, pcorrected = 0.029) and significantly higher MD in a global measure of thalamic radiations (β = 0.029, pcorrected = 0.021), as well as higher MD in the superior (β = 0.034, pcorrected = 0.039) and inferior (β = 0.029, pcorrected = 0.043) longitudinal fasciculus and in the anterior (β = 0.025, pcorrected = 0.046) and superior (β = 0.027, pcorrected = 0.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts.ConclusionsOur findings indicate that variation in the NETRIN1 signaling pathway may confer risk for MDD through effects on thalamic radiation white matter microstructure.

scholarly journals Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xingxing Zhu ◽  
Joey Ward ◽  
Breda Cullen ◽  
Donald M. Lyall ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Structure ◽  
Association Studies ◽  
Anterior Cingulate ◽  
White Matter Integrity ◽  
Grey Matter Volume ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Matter Volume

AbstractAnhedonia is a core symptom of multiple psychiatric disorders and has been associated with alterations in brain structure. Genome-wide association studies suggest that anhedonia is heritable, with a polygenic architecture, but few studies have explored the association between genetic loading for anhedonia—indexed by polygenic risk scores for anhedonia (PRS-anhedonia)—and structural brain imaging phenotypes. Here, we investigated how anhedonia and PRS-anhedonia were associated with brain structure within the UK Biobank cohort. Brain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness (CT) and white matter integrity) were analysed using linear mixed models in relation to anhedonia and PRS-anhedonia in 19,592 participants (9225 males; mean age = 62.6 years, SD = 7.44). We found that state anhedonia was significantly associated with reduced total grey matter volume (GMV); increased total white matter volume (WMV); smaller volumes in thalamus and nucleus accumbens; reduced CT within the paracentral cortex, the opercular part of inferior frontal gyrus, precentral cortex, insula and rostral anterior cingulate cortex; and poorer integrity of many white matter tracts. PRS-anhedonia was associated with reduced total GMV; increased total WMV; reduced white matter integrity; and reduced CT within the parahippocampal cortex, superior temporal gyrus and insula. Overall, both state anhedonia and PRS-anhedonia were associated with individual differences in multiple brain structures, including within reward-related circuits. These associations may represent vulnerability markers for psychopathology relevant to a range of psychiatric disorders.

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