Supplement to KCTD8 gene and brain growth in adverse intrauterine environment: a genome-wide association study.
Paus T, Bernard M, Chakravarty MM, Davey Smith G, Gillis J, Lourdusamy A, Melka MG, Leonard G, Pavlidis P, Perron M, Pike GB, Richer L, Schumann G, Timpson N, Toro R, Veillette S, Pausova Z
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.
Expression data and coexpression (etc) can be accessed at:
where “###” is the experiment number given, e.g., 1188
|Expression Experiment ID Numbers:||Experiment Names:|
The fetal coexpression data for Kctd8 is given by a score for each gene (higher, more highly coexpressed) between 0 and 1:
Fetal coexpression for kctd8 (genes are shown in order of decreasing coexpression, scores are relative ranks)
Gene subnetwork shown (of genes coexpressed with KCTD8)
Human Fetal Brain GO enrichment for KCTD8 (relative to enrichment for each other gene)