This project seeks to replicate findigns obtained in the Saguenay Youth Study on the relathionship between genetic variation in KCTD8 and brain size in offspring exposed to maternal smoking during pregnancy (see below for the summary).

We propose to use head circumference at birth as a proxy of brain size.

"The most dramatic growth of the human brain occurs in utero and during the first two years of post-natal life. Genesis of the cerebral cortex involves cell proliferation, migration and programmed cell-death (apoptosis), all of which may be influenced by prenatal environment. Here we show that a particular variant of KCTD8, a gene involved in tetramerisation of potassium channels, is associated with brain size in females (top single-nucleotide polymorphism in a genome-wide scan: rs716890, p=5.40E-09). Furthermore, we found that KCTD8 interacts with prenatal exposure to maternal cigarette smoking during pregnancy vis-a-vis cortical area and cortical folding: in exposed girls only, KCTD8 genotype explains up to 21% of the phenotype. We speculate that KCTD8 moderates adverse effects of smoking during pregnancy (hypoxia, flow of nutrients) on brain development via apoptosis triggered by low intra-cellular levels of potassium, possibly reducing the number of progenitor cells and, in turn, cortico-genesis in the exposed individuals." (From Paus et al., in preparation).