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

View ORCID ProfileHeidi Foo, Anbupalam Thalamuthu, Jiyang Jiang, Forrest C. Koch, Karen A. Mather, Wei Wen, Perminder S. Sachdev
doi: https://doi.org/10.1101/2020.09.17.268029
Heidi Foo
aCentre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, New South Wales 2052, Sydney, Australia
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  • For correspondence: heidi.foo@student.unsw.edu.au
Anbupalam Thalamuthu
aCentre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, New South Wales 2052, Sydney, Australia
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Jiyang Jiang
aCentre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, New South Wales 2052, Sydney, Australia
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Forrest C. Koch
aCentre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, New South Wales 2052, Sydney, Australia
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Karen A. Mather
aCentre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, New South Wales 2052, Sydney, Australia
bNeuroscience Research Australia, Randwick, New South Wales 2031, Sydney, Australia
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Wei Wen
aCentre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, New South Wales 2052, Sydney, Australia
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Perminder S. Sachdev
aCentre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, New South Wales 2052, Sydney, Australia
cNeuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Randwick, New South Wales 2031, Sydney, Australia
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Abstract

This is the first study investigating the genetics of weighted functional brain network graph theory measures from 18,445 participants of the UK Biobank (44-80 years). The eighteen measures studied showed low heritability (mean h2SNP =0.12) and were highly genetically correlated. Genome-wide association studies for these measures observed 14 significant variants associated with strength of somatomotor and limbic networks. These intergenic variants were located near the PAX8 gene on chromosome 2. Gene-based analyses identified five significantly associated genes for five of the network measures, which have been implicated in sleep duration, neuronal differentiation/development, cancer, and susceptibility to neurodegenerative diseases. Genetic correlations with other traits were examined and significant correlations were observed with sleep measures and psychiatric symptoms. Further analysis found that somatomotor network strength was phenotypically associated with sleep duration and insomnia. Single nucleotide polymorphism (SNP) and gene level associations with functional network measures were identified, which may help uncover novel biological pathways relevant to human brain functional network integrity and diseases that affect it.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 17, 2020.
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Novel genetic variants associated with brain functional networks in 18,445 adults from the UK Biobank
Heidi Foo, Anbupalam Thalamuthu, Jiyang Jiang, Forrest C. Koch, Karen A. Mather, Wei Wen, Perminder S. Sachdev
bioRxiv 2020.09.17.268029; doi: https://doi.org/10.1101/2020.09.17.268029
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Novel genetic variants associated with brain functional networks in 18,445 adults from the UK Biobank
Heidi Foo, Anbupalam Thalamuthu, Jiyang Jiang, Forrest C. Koch, Karen A. Mather, Wei Wen, Perminder S. Sachdev
bioRxiv 2020.09.17.268029; doi: https://doi.org/10.1101/2020.09.17.268029

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