A Chromatin Catalog for the Interpretation of Genetic Associations of Psychiatric Disorders

Giusti‐Rodríguez, Paola; Lu, Leina; Crowley, Cheynna; Bryois, Julien; Liu, Huan; Sariaslan, Amir; Jurić, Ivan; Martin, Joshua S.; Ancalade, NaEshia; DeCristo, Daniela M.; Stockmeier, Craig A.; Hu, Ming; Jin, Fulai; Li, Yun; Sullivan, Patrick F.

doi:10.1016/j.euroneuro.2017.08.251

Cited by 2 publications

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“…Mapping based on eQTLs relied on known associations between SNPs and the gene expression of genes within a 1-Mb window, from BRAINEAC frontal, occipital, temporal and cerebral cortex ( Ramasamy et al, 2014 ), GTEx v8 cerebral cortex ( GTEx Consortium, 2020 ) and xQTLServer dorsolateral prefrontal cortex ( Ng et al, 2017 ). Chromatin interaction mapping was based on established 3D DNA-DNA interactions between SNP and gene regions from Hi-C databases in cortex tissue [PsychENCODE by D. Wang et al (2018) , Giusti-Rodriguez et al (2019) and GSE87112 ( Schmitt et al, 2016 )]. To restrict chromatin interaction mapping to plausible biological interactions, we only included interactions where one region overlapped with an enhancer [as predicted by the Roadmap Epigenomics Consortium (2015) in cortex tissue] and the other region overlapped with a promoter (250 bp upstream to 500 bp downstream of the transcription start site as well as predicted by the Roadmap Epigenomics project in cortex tissue).…”

Section: Methodsmentioning

confidence: 99%

The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

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et al. 2023

eNeuro

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Functional connectivity within resting-state networks (RSN-FC) is vital for cognitive functioning. RSN-FC is heritable and partially translates to the anatomical architecture of white matter, but the genetic component of structural connections of RSNs (RSN-SC) and their potential genetic overlap with RSN-FC remain unknown. Here we perform genome-wide association studies (Ndiscovery=24,336; Nreplication=3,412) and annotation on RSN-SC and RSN-FC. We identify genes for visual network-SC that are involved in axon guidance and synaptic functioning. Genetic variation in RSN-FC impacts biological processes relevant to brain disorders that previously were only phenotypically associated with RSN-FC alterations. Correlations of the genetic components of RSNs are mostly observed within the functional domain, whereas less overlap is observed within the structural domain and between the functional and structural domains. This study advances the understanding of the complex functional organization of the brain and its structural underpinnings from a genetics viewpoint.Significance StatementBrain regions with synchronized activity can be clustered into distinct networks. We investigate which genetic effects contribute to structural and functional connectivity within seven networks and assess their degree of shared genetic signal. Multiple genetic effects are identified and highlight relevant biological processes for brain connectivity and brain disorders related to the networks. Overlap between the genetics of network connectivity is mostly observed within the functional domain. These results advance our biological understanding of the complex functional organisation of the brain and its structural underpinnings, and their relevance for the genetics of neuropsychiatry.

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Section: Methodsmentioning

confidence: 99%

The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

Tissink

Werme

Lange

et al. 2023

eNeuro

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show abstract

“…Mapping based on eQTLs relied on known associations between SNPs and the gene-expression of genes within a 1Mb window, from BRAINEAC 81 (frontal, occipital, temporal, cerebral cortex), GTEx v8 82 cerebral cortex and xQTLServer 83 dorsolateral prefrontal cortex. Chromatin interaction mapping was based on established 3D DNA-DNA interactions between SNP and gene regions from Hi-C databases in cortex tissue (PsychENCODE 84 , Giusti-Rodriguez et al 85 , and GSE87112 86 ). To restrict chromatin interaction mapping to plausible biological interactions, we only included interactions where one region overlapped with an enhancer (as predicted by the Roadmap Epigenomics project 87 in cortex tissue) and the other region overlapped with a promoter (250 bp upstream to 500 bp downstream of the transcription start site as well as predicted by the Roadmap Epigenomics project in cortex tissue).…”

Section: Methodsmentioning

confidence: 99%

Specificity and overlap in the genetic architectures of functional and structural connectivity within cerebral resting-state networks

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et al. 2022

Preprint

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The functional connectivity and dynamics of resting-state networks (RSN-FC) are vital for cognitive functioning. RSN-FC is heritable and partially translates to the anatomical architecture of white matter, but the genetic component of structural connections of RSNs (RSN-SC) and their potential genetic overlap with RSN-FC remains unknown. Here we perform genome-wide association studies (Ndiscovery=24,336; Nreplication=3,412) and in silico annotation on RSN-SC and RSN-FC. We identify the first genes for visual network-SC, that are involved in axon guidance and synaptic functioning and show that genetic variation in RSN-FC impacts biological processes related to brain disorders that have previously been associated with FC alterations in those same RSNs. Correlations of the genetic components of RSNs are mostly observed within the functional domain, whereas less overlap is observed within the structural domain and between the functional and structural domains. This study advances the understanding of the complex functional organization of the brain and its structural underpinnings from a genetics viewpoint.

show abstract

A Chromatin Catalog for the Interpretation of Genetic Associations of Psychiatric Disorders

Cited by 2 publications

References 0 publications

The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

The Genetic Architectures of Functional and Structural Connectivity Properties within Cerebral Resting-State Networks

Specificity and overlap in the genetic architectures of functional and structural connectivity within cerebral resting-state networks

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