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:10.1038/s41598-021-94182-9

Cited by 10 publications

(11 citation statements)

References 71 publications

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“…These data are consistent with the aging process resulting in changes in sleep habits and high blood pressure [20,63], both of which have been linked to functional connectivity changes [35,64,65]. The PAX8 protein has also been associated to the regulation of multiple genes involved in thyroid hormone synthesis, which is necessary for brain development and function, for example, through processes such as neuronal differentiation, synaptogenesis, and dendritic proliferation [35]. All functional measures associated with the PAX8 gene demonstrated substantial colocalization with the FoxD4L1 gene, which is similarly implicated in processes that promote the onset of neural differentiation [66].…”

Section: Discussionsupporting

confidence: 86%

“…Interestingly, this locus has been associated with sleep efficiency, diastolic blood pressure, insomnia, and sleep length [37]. These data are consistent with the aging process resulting in changes in sleep habits and high blood pressure [20, 63], both of which have been linked to functional connectivity changes [35, 64, 65]. The PAX8 protein has also been associated to the regulation of multiple genes involved in thyroid hormone synthesis, which is necessary for brain development and function, for example, through processes such as neuronal differentiation, synaptogenesis, and dendritic proliferation [35].…”

Section: Discussionsupporting

confidence: 52%

“…4 and Supplementary Figure S7). A locus near Paired Box 8 (PAX8 ), a gene involved in sleep efficiency, diastolic blood pressure, development and vulnerability to neurodegenerative diseases [35][36][37], showed an association with the majority of functional connectivity measures, including multilayer and multiplex clustering, as well as all single-layer measures. Colocalization analysis with eQTL summary statistics of 49 tissues in GTEx project and brain tissues in BrainSeq, ROSMAP, Braineac2 and CommonMind datasets (see Methods, section Colocalization) [38][39][40][41][42][43], suggests a consistent strong colocalization between this locus and gene expression patterns of Immunoglobulin Kappa Variable 1/OR2-108 (IGKV1OR2-108 ), COBW domain-containing protein 2 (CBWD2 ) and Forkhead Box D4 Like 1 (FOXD4L1 ) over the multilayer and multiplex clustering coefficients, average positive and negative connectivity and all singlelayer functional measures (Supplementary Table S8).…”

Section: Resultsmentioning

confidence: 99%

“…All functional measures associated with the PAX8 gene demonstrated substantial colocalization with the FoxD4L1 gene, which is similarly implicated in processes that promote the onset of neural differentiation [66]. They also demonstrated colocalization with CBWD2 , which has been linked to sleep duration [35], and IGKV1OR2-108 , which has been found to be elevated in the livers of type 2 diabetes patients [67] and can lead to abnormal functional connectivity [68].…”

Section: Discussionmentioning

confidence: 99%

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Sex differences in functional network topology over the course of aging in 37543 UK Biobank participants

Mijalkov

Veréb

Jamialahmadi

et al. 2022

Preprint

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Aging is a major risk factor for cardiovascular and neurodegenerative disorders, with considerable societal and economic implications. Healthy aging is accompanied by changes in connectivity between and within resting-state functional networks, however, there is no consensus on the impact of sex on these age-related alterations. Here, in a large cross-sectional sample of 37543 UK Biobank participants, we show that multilayer measures that capture the interaction between positive and negative connections provide crucial information on the impact of sex on age-related changes in network topology, being closely related to cognitive, structural, and cardiovascular risk factors that have been shown to differ between men and women. We also provide additional insights into the genetic influences on multilayer connectivity changes that occur during aging. Our findings indicate that multilayer measures contain previously unknown information on the relationship between sex and age, opening up new avenues for research into functional brain connectivity in aging.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Sex differences in functional network topology over the course of aging in 37543 UK Biobank participants

Mijalkov

Veréb

Jamialahmadi

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Studies have shown that genetic factors significantly contribute to RSN-FC ( H 2 = 20-40%) 5–10 . Genome-wide association studies (GWAS) on FC graph theory measures 11 and extrinsic and intrinsic functional organization 12 of RSNs have identified the first genetic variants and genes that make up this genetic component (mean 11 ), and show genetic overlap between FC and psychiatric disorders 13 . RSNs were traditionally discovered based on FC 2 and correlate with the structural connectivity (SC) architecture of white matter in the brain 14–16 to varying degrees across RSNs 17 .…”

Section: Introductionmentioning

confidence: 99%

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

Tissink

Werme

Lange

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.

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Functionally annotated electrophysiological neuromarkers of healthy ageing and memory function

Auer,

Goldthorpe,

Peach

et al. 2024

Human Brain Mapping

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The unprecedented increase in life expectancy presents a unique opportunity and the necessity to explore both healthy and pathological aspects of ageing. Electroencephalography (EEG) has been widely used to identify neuromarkers of cognitive ageing due to its affordability and richness in information. However, despite the growing volume of data and methodological advancements, the abundance of contradictory and non‐reproducible findings has hindered clinical translation. To address these challenges, our study introduces a comprehensive workflow expanding on previous EEG studies and investigates various static and dynamic power and connectivity estimates as potential neuromarkers of cognitive ageing in a large dataset. We also assess the robustness of our findings by testing their susceptibility to band specification. Finally, we characterise our findings using functionally annotated brain networks to improve their interpretability and multi‐modal integration. Our analysis demonstrates the effect of methodological choices on findings and that dynamic rather than static neuromarkers are not only more sensitive but also more robust. Consequently, they emerge as strong candidates for cognitive ageing neuromarkers. Moreover, we were able to replicate the most established EEG findings in cognitive ageing, such as alpha oscillation slowing, increased beta power, reduced reactivity across multiple bands, and decreased delta connectivity. Additionally, when considering individual variations in the alpha band, we clarified that alpha power is characteristic of memory performance rather than ageing, highlighting its potential as a neuromarker for cognitive ageing. Finally, our approach using functionally annotated source reconstruction allowed us to provide insights into domain‐specific electrophysiological mechanisms underlying memory performance and ageing.Highlights We provide an open and reproducible pipeline with a comprehensive workflow to investigate static and dynamic EEG neuromarkers. Neuromarkers related to neural dynamics are sensitive and robust. Individualised alpha power characterises cognitive performance rather than ageing. Functional annotation allows cross‐modal interpretation of EEG findings.

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

Cited by 10 publications

References 71 publications

Sex differences in functional network topology over the course of aging in 37543 UK Biobank participants

Sex differences in functional network topology over the course of aging in 37543 UK Biobank participants

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

Functionally annotated electrophysiological neuromarkers of healthy ageing and memory function

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