Rotman Research Institute, University of Toronto, Toronto, Ontario M6A 2E1, Canada.
Cereb Cortex. 2012 Nov;22(11):2634-42. doi: 10.1093/cercor/bhr350. Epub 2011 Dec 9.
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.
人类大脑的发育在子宫内和出生后的前 2 年最为显著。大脑皮层的形成涉及细胞增殖、迁移和细胞凋亡，所有这些过程都可能受到产前环境的影响。在这里，我们发现 KCTD8（钾通道四聚化结构域 8）的变异与女性青少年的大脑大小有关（rs716890，P = 5.40×10(-09)）。此外，我们发现 KCTD8 基因座与产前母亲吸烟暴露对视皮质面积和皮质折叠相互作用：仅在暴露于吸烟的女孩中，KCTD8 基因座可以解释高达 21%的变异。我们使用 7 岁时的头围作为大脑大小的替代指标，在一个独立的样本中复制了这种基因-环境相互作用。我们推测，KCTD8 可能通过细胞内低钾水平触发的细胞凋亡，调节怀孕期间吸烟对大脑发育的不利影响，从而可能减少祖细胞的数量。
