Novel genetic variants associated with brain functional networks in 18,445 adults from the UK Biobank

Foo, Heidi; Thalamuthu, Anbupalam; Jiang, Jiyang; Koch, Forrest; Mather, Karen A.; Wang, Wen; Sachdev, Perminder S.

doi:10.1101/2020.09.17.268029

Cited by 2 publications

(1 citation statement)

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“…=0.09) (Wei et al, 2019) and for a set of topological measures derived from fMRI networks (mean ℎ '(! " =0.12), including global efficiency, characteristic path length and transitivity (Foo et al, 2020). These findings align with classical twin results to suggest a lower level of genetic influence on functional connectivity compared to structural connectivity.…”

Section: Association Analysessupporting

confidence: 87%

Where the genome meets the connectome: understanding how genes shape human brain connectivity

Arnatkevičiūtė¹,

Fulcher²,

Bellgrove³

et al. 2021

Preprint

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The integration of modern neuroimaging methods with genetically informative designs and data can shed light on the molecular mechanisms underlying the structural and functional organisation of the human connectome. Here, we review studies that have investigated the genetic basis of human brain network structure and function through three complementary frameworks: (1) the quantification of phenotypic heritability through classical twin designs; (2) the identification of specific DNA variants linked to phenotypic variation through association and related studies; and (3) the analysis of correlations between spatial variations in imaging phenotypes and gene expression profiles through the integration of neuroimaging and transcriptional atlas data. We consider the basic foundations, strengths, limitations, and discoveries associated with each approach. We present converging evidence to indicate that anatomical connectivity is under stronger genetic influence than functional connectivity and that genetic influences are not uniformly distributed throughout the brain, with phenotypic variation in certain regions and connections being under stronger genetic control than others. We also consider how the combination of imaging and genetics can be used to understand the ways in which genes may drive brain dysfunction in different clinical disorders.

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Section: Association Analysessupporting

confidence: 87%

Where the genome meets the connectome: understanding how genes shape human brain connectivity

Arnatkevičiūtė¹,

Fulcher²,

Bellgrove³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

Genome-wide association study of the human brain functional connectome reveals strong vascular component underlying global network efficiency

Bell

Tozer

Markus

2022

Sci Rep

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Complex brain networks play a central role in integrating activity across the human brain, and such networks can be identified in the absence of any external stimulus. We performed 10 genome-wide association studies of resting state network measures of intrinsic brain activity in up to 36,150 participants of European ancestry in the UK Biobank. We found that the heritability of global network efficiency was largely explained by blood oxygen level-dependent (BOLD) resting state fluctuation amplitudes (RSFA), which are thought to reflect the vascular component of the BOLD signal. RSFA itself had a significant genetic component and we identified 24 genomic loci associated with RSFA, 157 genes whose predicted expression correlated with it, and 3 proteins in the dorsolateral prefrontal cortex and 4 in plasma. We observed correlations with cardiovascular traits, and single-cell RNA specificity analyses revealed enrichment of vascular related cells. Our analyses also revealed a potential role of lipid transport, store-operated calcium channel activity, and inositol 1,4,5-trisphosphate binding in resting-state BOLD fluctuations. We conclude that that the heritability of global network efficiency is largely explained by the vascular component of the BOLD response as ascertained by RSFA, which itself has a significant genetic component.

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Novel genetic variants associated with brain functional networks in 18,445 adults from the UK Biobank

Cited by 2 publications

References 62 publications

Where the genome meets the connectome: understanding how genes shape human brain connectivity

Where the genome meets the connectome: understanding how genes shape human brain connectivity

Genome-wide association study of the human brain functional connectome reveals strong vascular component underlying global network efficiency

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