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
Brain Struct Funct. 2018-12-05; 224(2): 847-857
DOI: 10.1007/s00429-018-1808-9

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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 3435
subjects for discovery and replication samples, respectively). We found that the
heritability of the sulcal opening ranges from 15 to 45% (SE = 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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