The A-to-T SNP rs7794745 in the CNTNAP2 gene was found to be associated with increased risk of autism (see Arking et al., 2008). Specifically, the TT genotype, found in about 15% of individuals, increases these folks’ risk by about 1.2-1.7-fold. Sure enough, when I checked my 23andMe profile, I found that I’m one of these TT risk-bearing individuals. Interesting, although not alarming since me and my kids are beyond the age where one typically worries about autism. Still, one can wonder if such a risk factor might have exerted some influence on the development of my brain?
The recent paper by Tan et al., “Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2” [doi:10.1016/j.neuroimage.2010.02.018 ] suggests there may be subtle, but still profound influences of the TT genotype on brain development in healthy individuals. According to the authors, “homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation.”
The FA (fractional anisotropy – a measurement of white-matter or myelination) results are consistent with a role of CNTNAP2 in the establishment of synaptic contacts and other cell-cell contacts especially at Nodes of Ranvier – which are critical for proper function of white-matter tracts that support rapid, long-range neural transmission. Indeed, more severe mutations in CNTNAP2 have been associated with cortical dysplasia and focal epilepsy (Strauss et al., 2006).
Subtle changes perhaps influencing long-range information flow in my brain – wow!
More on CNTNAP2 … its evolutionary history and role in language development.