KCTD8 gene and brain growth in adverse intrauterine environment: A genome-wide association study

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:	Gillis, Jesse
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:	Publisher
URI:	https://repository.cshl.edu/id/eprint/28082

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