The complex genetics of musical talent

Humans create a rich variety of music, and most people enjoy music in some form. In fact, music is so interwoven into humanity that the ability to perceive and create music is present in all human societies known to date. Archeological evidence of musical instruments from 40,000 years ago indicates that humans have valued the ability to generate music for at least that long, and probably longer. Moreover, musical ability is likely under positive selection in the human population. Does that mean musicians are therefore born instead of made?

You don't need to be a member of the Jackson Five or the von Trapp Family Singers to recognize that musical ability tends to run in families. This could suggest that musicality is inherited, but it could also suggest that early exposure to music (as would happen in a musical family) drives increased aptitude. Up until the past decade or so, segregating these two hypotheses was fairly difficult, but more refined genomic and computational tools and a better understanding of the human genome have allowed for some interesting findings related to the genetics of musical talent.

 Tuning in to the inner earBasile Tarchini, Ph.D., is working to understand the basic mechanisms underlying hair cell development, with the goal of restoring hearing following injury.tuning-in-to-the-inner-ear

To be sure, musical talent is not a very quantifiable trait, which can make for a lot of noise in genome-wide association studies looking for shared variants of significance. Instead, many researchers study the genetics of musical ability through the lens of absolute pitch (also known as “perfect pitch”). Absolute pitch (AP) is ability to instantaneously identify or recreate a given musical note without the benefit of a reference tone. While rare, this is a quantifiable — and complex — trait. AP is thought to be both environmentally and genetically influenced.

Environmentally, in a relatively large, self-reporting survey of musicians, 40% of respondents who began musical training at the age of 4 or younger reported possession of AP, and the percentage decreased steadily as the age of first training increased, to 3% of those who began studying music at the age of nine or older. Thus, very early exposure to musical training may predispose children toward AP. However, these types of surveys cannot parse whether children who started musical training at such a young age were more “naturally gifted” than the children who started later.

Similar to general musical talent, it has long been described that AP runs in families, and there are several groups (Ashkenazi Jewish, for example) with much higher rates of AP than the general population. For instance, in 2001 Gregersen et al. found that Chinese, Korean, and Japanese music students had a significantly higher incidence of AP (47.5%) compared to Caucasian students (9%). But again, these associations lack for controlled studies of how and when AP develops, so whether this trend is indicative of inheritance is speculative.

To get at whether AP is truly inherited, familial and ethnically parsed cohorts have been studied in detail to find regions of genome shared among the musically gifted. Looking at 73 multiplex families (those with multiple family members that share the trait in question) Theusch et al. found 4 large chromosomal regions linked to AP, although none were strong enough to reach statistical significance among all the families. The strongest link was found on chromosome 8q in the 45 families of European ancestry. Genes of interest in this area include ADCY8 (adenylate cyclase 8), which encodes a membrane bound enzyme that catalyzes the formation of cyclic AMP from ATP, a pretty basic cellular process. However, this particular gene is expressed exclusively in the brain, and its activity has been linked to memory and learning, which lends some plausibility to the link between protein activity and the generation of AP. While this discovery is intriguing, making definitive links between the genome and AP are hampered by several factors, including the likelihood of multiple genes involved, the fact that not every family member has musical training, and the expectation of incomplete penetrance.

Another study found a genetic link between AP and synesthesia in a cohort of 768 subjects with self-documented AP. Synesthesia is a rare cognitive trait in which the stimulation of one sensory pathway leads to the involuntary stimulation of a second sensory pathway. The most common form links sound and color, although sound and taste are also described. Like AP, synesthesia runs in families. Gregersen et al. found 20% of their AP cohort also experienced synesthesia, which is significantly enriched compared to the general population (estimated at 0.2 – 0.005%). Here, the researchers linked the presence of both traits to a region on chromosome 6q that encodes 73 genes, including several with roles in neurodevelopment. However, more fine-grained analysis is needed to determine if any of these genes significantly impact either trait.

The fact that several studies connect musical ability (or more specifically, the cognitive trait AP) to genomic regions, but each study identifies different regions, further supports that idea that multiple genes and pathways are involved in this complex human characteristic. And as with many human traits, genetics are not everything. Everyone knows how you get to Carnegie Hall: You practice!

Sara Cassidy, Ph.D. is a lazy practitioner of the piano and the guitar, and is a senior scientific writer at The Jackson Laboratory for Genomic Medicine.