When Sir Francis Galton first described the “peculiar habit of mind” we now call synaesthesia, he noted that it often runs in families. Modern techniques have confirmed that the condition does indeed have a strong genetic component – more than 40% of synaesthetes have a first-degree relative – a parent, sibling or offspring – who also has synaesthesia, and families often contain multiple synaesthetes.
Synaesthesia is known to affect females more than males, and although the female predominance of the condition is now known to have been exaggerated, the condition is presumed to be linked to the X chromosome. A number of genetic studies also support the theory that a single gene is responsible for synaesthesia, and that it is inherited in a dominant manner (in other words, just one copy of the gene, inherited from either parent, is sufficient to cause it).
Researchers from the University of Oxford have now conducted the first genome-wide search for genes linked to the condition. In the American Journal of Human Genetics, they report the identification of a number of genes that are likely to be involved in auditory-visual synaesthesia, in which sounds are perceived as colours. The study reveals also that synaesthesia is not X-linked, and that the genetics of this form of synaesthesia – and probably that of other forms – is far more complex than previously thought.
A group led by Julian Asher of the Wellcome Trust Centre for Human Genetics, in collaboration with Simon Baron-Cohen‘s group at Cambridge, studied 43 large families, all of which include multiple members with auditory-visual synaesthesia. They recruited a total of 196 individuals, of which 121 were synaesthetes as confirmed by a questionnaire designed to test for the intensity and genuinesness of the synaesthetic experience.
The researchers obtained DNA samples from each participant, and analysed more than 400 microsatellites dispersed across all the chromosomes. Microsatellites consist of very short sequences which are repeated multiple times; each allele, or variant, of a given gene contains a unique number of repeats, and this number often varies between individuals. These sequences are therefore often used to identify genetic variation in humans, as different alleles of the same gene can be distinguished from one another. In this case, however, the researchers searched for evidence of genetic linkage.
By comparing the DNA samples from different generations of synaesthetes from the same family, they identified the microsatellites which are inherited together. Rather than identifying specific genes, this analysis identified four distinct chromosomal regions located on three different chromosomes, all containing genes of interest. These regions are known to contain genes associated with a variety of disorders, including autism, dyslexia and epilepsy.
One of the candidate genes encodes the transcription factor TBR1, which regulates the activity of a number of other genes, including reelin, a signalling protein that is critical for the proper development of the cerebral cortex; another plays a role in several different developmental processes, including axon guidance, the process by which extending neuronal processes find their correct destination; and a third candidate, a sodium channel protein called SCN2A, is involved in regulating the electrical actvity of nerve cells and has been implicated in epilepsy. The region with the strongest linkage, which located on chromosome 2, is known to contain a gene associated with autism. Like synaesthesia, autism involves sensory and perceptual abnormalities, and autistics often report synaesthesia-like symptoms.
Neuroimaging shows that the connections between the brain’s sensory pathways are both denser and more active in synaesthetes than in non-synaesthetes. The condition is now viewed as being developmental in origin, and it is thought that newly-established connections, which would otherwise be “pruned” during development, remain in place, and perhaps become overactive. The results of the new study therefore fit nicely with current thinking about the neural bases of synaesthesia. Specific combinations of alleles of the identified candidate genes could feasibly lead to subtle changes in developmental processes which ultimately result in alterations in neural architecture and activity thought to be involved in the condition.
As well as revealing the complexity of the genetics of synaesthesia, this study also shows that it can be inherited in a number of different ways (that is, by inheriting different combinations of alleles). The eventual identification and proper classification of all the candidate genes will inevitably lead to a better understanding not only of synaesthesia and the other conditions with which they are associated, but also of their roles in cognition more generally. The authors also suggest that advances in our knowledge of synaesthetic perceptions “may even shed light on the neural basis of consciousness”.