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Genome-wide association studies of brain structure and function in the UK Biobank

View ORCID ProfileLloyd T. Elliott, View ORCID ProfileKevin Sharp, View ORCID ProfileFidel Alfaro-Almagro, Sinan Shi, View ORCID ProfileKarla Miller, View ORCID ProfileGwenaëlle Douaud, View ORCID ProfileJonathan Marchini, View ORCID ProfileStephen Smith
doi: https://doi.org/10.1101/178806
Lloyd T. Elliott
1Department of Statistics, University of Oxford, Oxford, UK.
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Kevin Sharp
1Department of Statistics, University of Oxford, Oxford, UK.
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Fidel Alfaro-Almagro
2FMRIB, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK.
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Sinan Shi
1Department of Statistics, University of Oxford, Oxford, UK.
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Karla Miller
2FMRIB, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK.
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Gwenaëlle Douaud
2FMRIB, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK.
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Jonathan Marchini
1Department of Statistics, University of Oxford, Oxford, UK.
3The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
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  • For correspondence: marchini@stats.ox.ac.uk steve@fmrib.ox.ac.uk
Stephen Smith
2FMRIB, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK.
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  • For correspondence: marchini@stats.ox.ac.uk steve@fmrib.ox.ac.uk
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Summary

The genetic basis of brain structure and function is largely unknown. We carried out genome-wide association studies of 3,144 distinct functional and structural brain imaging derived phenotypes in UK Biobank (discovery dataset 8,428 subjects). We show that many of these phenotypes are heritable. We identify 148 clusters of SNP-imaging associations with lead SNPs that replicate at p<0.05, when we would expect 21 to replicate by chance. Notable significant and interpretable associations include: iron transport and storage genes, related to changes in T2* in subcortical regions; extracellular matrix and the epidermal growth factor genes, associated with white matter micro-structure and lesion volume; genes regulating mid-line axon guidance development associated with pontine crossing tract organisation; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide new insight into the genetic architecture of the brain with relevance to complex neurological and psychiatric disorders, as well as brain development and aging. The full set of results is available on the interactive Oxford Brain Imaging Genetics (BIG) web browser.

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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. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 29, 2018.
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Genome-wide association studies of brain structure and function in the UK Biobank
Lloyd T. Elliott, Kevin Sharp, Fidel Alfaro-Almagro, Sinan Shi, Karla Miller, Gwenaëlle Douaud, Jonathan Marchini, Stephen Smith
bioRxiv 178806; doi: https://doi.org/10.1101/178806
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Genome-wide association studies of brain structure and function in the UK Biobank
Lloyd T. Elliott, Kevin Sharp, Fidel Alfaro-Almagro, Sinan Shi, Karla Miller, Gwenaëlle Douaud, Jonathan Marchini, Stephen Smith
bioRxiv 178806; doi: https://doi.org/10.1101/178806

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