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eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data

View ORCID ProfileYann Le Guen, Cathy Philippe, Denis Riviere, Hervé Lemaitre, Antoine Grigis, Clara Fischer, Ghislaine Dehaene-Lambertz, Jean-François Mangin, Vincent Frouin
doi: https://doi.org/10.1101/386821
Yann Le Guen
UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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  • ORCID record for Yann Le Guen
Cathy Philippe
UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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Denis Riviere
UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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Hervé Lemaitre
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging & Psychiatry”, Faculté de médecine, Université Paris-Sud, Le Kremlin-Bicêtre; and Université Paris Descartes, Sorbonne Paris Cité, Paris, France
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Antoine Grigis
UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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Clara Fischer
UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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Ghislaine Dehaene-Lambertz
INSERM, UMR992, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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Jean-François Mangin
UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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Vincent Frouin
UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, France
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Abstract

The grey and white matter volumes are known to reduce with age. This cortical shrinkage is visible on magnetic resonance images and is conveniently identified by the increased volume of cerebrospinal fluid in the sulci between two gyri. Here, we replicated this finding using the UK Biobank dataset and studied the genetic influence on these cortical features of aging. We divided all individuals genetically confirmed of British ancestry into two sub-cohorts (12,162 and 3,435 subjects for discovery and replication samples, respectively). We found that the heritability of the sulcal opening ranges from 15 to 45% (s.e.= 4.8%). We identified 4 new loci that contribute to this opening, including one that also affects the sulci grey matter thickness. We identified the most significant variant (rs864736) on this locus as being an expression quantitative trait locus (eQTL) for the KCNK2 gene. This gene regulates the immune-cell into the central nervous system (CNS) and controls the CNS inflammation, which is implicated in cortical atrophy and cognitive decline. These results expand our knowledge of the genetic contribution to cortical shrinking and promote further investigation into these variants and genes in pathological context such as Alzheimer’s disease in which brain shrinkage is a key biomarker.

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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 4.0 International license.
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Posted August 07, 2018.
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eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data
Yann Le Guen, Cathy Philippe, Denis Riviere, Hervé Lemaitre, Antoine Grigis, Clara Fischer, Ghislaine Dehaene-Lambertz, Jean-François Mangin, Vincent Frouin
bioRxiv 386821; doi: https://doi.org/10.1101/386821
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eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data
Yann Le Guen, Cathy Philippe, Denis Riviere, Hervé Lemaitre, Antoine Grigis, Clara Fischer, Ghislaine Dehaene-Lambertz, Jean-François Mangin, Vincent Frouin
bioRxiv 386821; doi: https://doi.org/10.1101/386821

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