Paus, T., Bernard, M., Chakravarty, M. M., Davey Smith, G., Gillis, J., Lourdusamy, A., Melka, M. G., Leonard, G., Pavlidis, P., Perron, M., Pike, G. B., Richer, L., Schumann, G., Timpson, N., Toro, R., Veillette, S., Pausova, Z.
(2012)
KCTD8 gene and brain growth in adverse intrauterine environment: A genome-wide association study.
Cerebral Cortex, 22 (11).
pp. 2634-2642.
ISSN 10473211 (ISSN)
Abstract
The most dramatic growth of the human brain occurs in utero and during the first 2 years of postnatal life. Genesis of the cerebral cortex involves cell proliferation, migration, and apoptosis, all of which may be influenced by prenatal environment. Here, we show that variation in KCTD8 (potassium channel tetramerization domain 8) is associated with brain size in female adolescents (rs716890, P = 5.40 × 10 -09). Furthermore, we found that the KCTD8 locus interacts with prenatal exposure to maternal cigarette smoking vis-à-vis cortical area and cortical folding: In exposed girls only, the KCTD8 locus explains up to 21% of variance. Using head circumference as a proxy of brain size at 7 years of age, we have replicated this gene-environment interaction in an independent sample. We speculate that KCTD8 might modulate adverse effects of smoking during pregnancy on brain development via apoptosis triggered by low intracellular levels of potassium, possibly reducing the number of progenitor cells. © 2012 The Author.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
adolescence
brain
GWAS
pregnancy
potassium
adolescent
adult
apoptosis
article
birth weight
brain cortex
brain development
brain growth
brain size
child
female
gene locus
genetic association
human
image analysis
longitudinal study
magnet
major clinical study
male
maternal smoking
nerve cell
nuclear magnetic resonance imaging
parent
passive smoking
potassium channel tetramerization domain 8 gene
pregnant woman
priority journal |
| Subjects: |
bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
organs, tissues, organelles, cell types and functions > organs types and functions > brain
organism description > animal > developmental stage > child
organism description > animal > developmental stage
organism description > animal > developmental stage > fetal
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
organs, tissues, organelles, cell types and functions > organs types and functions |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Gillis Lab |
| Depositing User: |
Matt Covey
|
| Date: |
2012 |
| Date Deposited: |
04 Apr 2013 13:48 |
| Last Modified: |
04 Apr 2013 13:48 |
| PMCID: |
PMC3464418 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/28082 |
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