For some, musical notes conjure flashes of color, letters and numbers have their own particular hues, and certain sounds tickle. Researchers have reported these extraordinary cases of sensory mixing, called synesthesia—loosely translated to perceived together—for more than 130 years. But the molecular underpinnings of the vibrant experiences have been a complete mystery—until now.

With the help of three large families of synesthetes, researchers identified a smattering of genes that may help explain their mingled senses. Several of the genes were involved in making connections among neurons within and across various brain regions. And additional data suggested that these genes are active in regions of the brain involved in receiving and processing visual and auditory information while those regions develop.

The findings, published this week in PNAS, appear to support the hypothesis that synesthesia is caused by hyper-connectivity among brain regions that handle our senses. Essentially, the idea is that dense, trippy sensory networks load up with signals that may spill over to each other or that extra connections bridge the different sensory systems, breaking down their “modularity.”

The researchers behind the work—led by Simon Fisher at the Max Planck Institute for Psycholinguistics—are hopeful that the early genetic glimpse could help explain the sensational senses. They also speculate that such insights may one day help unravel other conditions that may involve brain-connectivity issues, such as autism.

Fisher and colleagues wrote that the study:

[F]ocused on relatively rare genetic variation occurring in families with multiple generations of synesthetes; assessing potential roles of common variation represents an intriguing question for the future.

For the study, the researchers collected genetic material from members of three families, sampling four or five people with clinically verified synesthesia across three generations in each family, as well as non-synesthetes. These families all had the same common type of synesthesia that couples sounds with colors. The families had been identified from the Cambridge Synesthesia Research Group database and were involved in previous genetic research, which also tried to unravel the genetics of the condition.

In their study, Fisher and colleagues focused on whole exome sequencing, which decodes the regions of DNA that are translated into proteins. Sifting through the code, the researchers picked out 37 gene variants that seemed to link to inherited synesthesia. None of those were the same across all synesthetes in all three families. This backs up the murky findings of the earlier genetic work from Cambridge that suggested there are many different genetic variations that can contribute to the condition.

But this time, the researchers were able to pinpoint specific genes. Six of those were known to be involved in cell migration and growth of nerve fibers, both essential in creating connections and networks in the brain. Based on data from earlier gene activity studies and protein-level surveys, the researchers found that these genes were active in sensory brain regions and active as those regions developed in early childhood.

The researchers speculate that the variation in brain connection development may “act in concert with early life experiences to form synesthetes’ unique secondary mappings (such as C♯ appearing orange, or B♭ as a deep brown).”

There’s a lot of work researchers will need to do to confirm that the identified genes are indeed involved in the condition—and to understand how. But “these results provide a molecular starting point for studies addressing the origins of healthy variation in sensory integration,” they conclude.

PNAS, 2018. DOI: 10.1073/pnas.1715492115 (About DOIs).