Dataset Information

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

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 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.

SUBMITTER: Le Guen Y

PROVIDER: S-EPMC6420450 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Le Guen Yann Y Philippe Cathy C Riviere Denis D Lemaitre Hervé H Grigis Antoine A Fischer Clara C Dehaene-Lambertz Ghislaine G Mangin Jean-François JF Frouin Vincent V

Brain structure & function 20181205 2

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 ...[more]

PMID: 30519892

Similar Datasets

Project description:BackgroundThe effects of insulin-like growth factor-1 (IGF-1) deficiency on cognitive decline have been consistently reported in animal studies, but the relationship between IGF-1 and human brain health remains controversial. Our study aimed to investigate the associations of serum IGF-1 concentrations with some brain-related disorders and neuroimaging features.MethodsThis prospective study included 369,711 participants (55.8 ± 8.1 years) from the UK biobank who had serum IGF-1 measured and were free from brain-related disorders of interest - dementia, stroke, and Parkinson's disease (PD) - at enrollment (2006-2010). Restricted cubic splines and Cox proportional hazards models were used to detect the associations between IGF-1 concentrations and brain-related diseases. In addition, general linear regressions were applied to explore the relationship between IGF-1 concentrations and neuroimaging features (volumes of white matter, grey matter, and hippocampus and white matter hyperintensity) among a sub-sample of 36,458 participants with magnetic resonance imaging data collected since 2014.ResultsDuring a median follow-up of 12.6 years, a total of 4,857 dementia, 6,240 stroke, and 2,116 PD cases were documented. The dose-response analyses yielded U-shaped relationships between IGF-1 concentrations and risks of dementia and stroke (P < 0.001 for non-linearity), with the lowest risks at 18 nmol/L and 26 nmol/L, respectively. A positive linear relationship was observed between IGF-1 concentrations and risk of PD (P = 0.163 for non-linearity). Moreover, neuroimaging analyses showed that higher IGF-1 concentrations were associated with greater volumes of white matter (β = 2.98 × 10-4, P < 0.001) and hippocampus (β = 3.37 × 10-4, P = 0.002) and smaller white matter hyperintensity (β = -3.12 × 10-3, P < 0.001).ConclusionsApart from the diverse associations with neuroimaging features, both low and high IGF-1 concentrations are associated with increased risks of dementia and stroke and higher IGF-1 concentrations are linked to a higher risk of PD, highlighting the potential of IGF-1 as a biomarker for risk stratification of brain health.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets