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

Authors
  • Paus, Tomás
  • Bernard, Manon
  • Chakravarty, M Mallar
  • Davey Smith, George
  • Gillis, Jesse
  • Lourdusamy, Anbarasu
  • Melka, Melkaye G
  • Leonard, Gabriel
  • Pavlidis, Paul
  • Perron, Michel
  • Pike, G Bruce
  • Richer, Louis
  • Schumann, Gunter
  • Timpson, Nicholas
  • Toro, Roberto
  • Veillette, Suzanne
  • Pausova, Zdenka
Type
Published Article
Journal
Cerebral Cortex
Publisher
Oxford University Press
Publication Date
Dec 22, 2011
Volume
22
Issue
11
Pages
2634–2642
Identifiers
DOI: 10.1093/cercor/bhr350
PMID: 22156575
PMCID: PMC3464418
Source
USPC - SET - SVS
License
Green

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.

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