Search for Genetic Variants Underlying Musical Aptitude and Related Traits
Liisa Ukkola‐Vuoti · Työväentutkimus Vuosikirja · 2013
Music perception and practice represents complex cognitive functions of the brain. There is an abundance of data about the neurophysiological effects of music on the human brain, but heritability and especially molecular studies have been lacking. The development of genome technologies and bioinformatics has enabled the identification of genetic variants underlying complex human traits. These methods can be applied to normal human traits like music perception and performance. Prior to this study, the first genome wide scan in the Finnish pedigrees suggested that musical aptitude is associated with several chromosomal areas in the human genome. High heritability of music test scores was also demonstrated. In order to further dissect the molecular genetic background of music related traits this thesis work focused on three phenotypes in music, musical aptitude, listening to music and creativity in music in the enlarged family material. For the aforementioned phenotypes functionally relevant candidate genes were analyzed, and novel genomic variants and candidate genes sought using genome-wide analysis of single nucleotide polymorphisms and structural variation (copy number variation; CNV). In this thesis, musical aptitude of each participant was defined using three music tests: the auditory structuring ability test (Karma Music test) and Seashore's pitch and time discrimination subtests. A combined music test score (COMB) was computed as the sum of the separate scores of the three individual test results. Information about other musical traits, creative functions in music and listening to music, and background information was collected using a web-based questionnaire. Both musical aptitude and creative functions in music showed to have strong genetic components, the heritability estimates were 0.44 and 0.84 respectively. On the average, the amount of time spent on active listening to music was 4.6 hours per week and passive 7.3 hours per week among the participants. Furthermore, high scores in music tests correlated with creative functions in music, and high amount of active listening to music correlated with the high level of music education. Five candidate genes, AVPR1A, SLC6A4, COMT, DRD2 and TPH1, were studied in musical aptitude, creativity in music and listening to music. All studied traits were associated with the arginine vasopressin receptor 1A (AVPR1A) gene, suggesting that the neurobiology of music perception and practice is likely to be related to pathways affecting social affiliation and communication. In the genome-wide CNV study several copy number variable regions containing genes that affect neurodevelopment, learning and memory were detected. The most promising of them was a deletion at 5q31.1 covering the protocadherin-α gene cluster (PCDHA) that was associated with low music test scores. PCDHA is involved in neural migration, differentiation and synaptogenesis. Creativity in music was associated with a duplication covering glucose mutarotase gene (GALM) at 2p22. A 1.3 Mb duplication was identified in a subject with low COMB scores overlapping the core linkage region of absolute pitch at 8q24. Genome-wide association analysis of creative functions in music showed association with several genes previously shown to be related to learning, memory, synaptic plasticity and neuropsychiatric disorders. The strongest association was detected with the cGMP-dependent protein kinase type I (PRKG1) gene at 10p21 that affects amygdala function, a brain area also induced by music. PRKG1 has previously been associated with schizophrenia and attention deficit hyperactivity disorder. In conclusion, our results suggest new candidate genes for musical aptitude and creativity in music. Being aware that musical aptitude is a complex phenotype affected by several predisposing alleles, this result, although interesting, is preliminary and may only partially explain the genetic background of musical aptitude. Further studies are needed to confirm the role of the candidate genes identified in musical aptitude and related traits.