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A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

Abstract

Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested. We performed a genome-wide scan in 76 pedigrees (767 individuals) characterized for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception. Using the Bayesian linkage and association approach implemented in program package KELVIN, especially designed for complex pedigrees, several single nucleotide polymorphisms (SNPs) near genes affecting the functions of the auditory pathway and neurocognitive processes were identified. The strongest association was found at 3q21.3 (rs9854612) with combined SP, ST and KMT test scores (COMB). This region is located a few dozen kilobases upstream of the GATA binding protein 2 (GATA2) gene. GATA2 regulates the development of cochlear hair cells and the inferior colliculus (IC), which are important in tonotopic mapping. The highest probability of linkage was obtained for phenotype SP at 4p14, located next to the region harboring the protocadherin 7 gene, PCDH7. Two SNPs rs13146789 and rs13109270 of PCDH7 showed strong association. PCDH7 has been suggested to play a role in cochlear and amygdaloid complexes. Functional class analysis showed that inner ear and schizophrenia-related genes were enriched inside the linked regions. This study is the first to show the importance of auditory pathway genes in musical aptitude.

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Acknowledgements

We are grateful to the families for their participation. We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070) for the generation of the genotype data. Daniel Borshagovski is thanked for information about the regulatory elements. Johanna Lumme is thanked for the artwork and Minna Varhala for her expert laboratory work. Funding for this study was provided by the Academy of Finland #13371, the Finnish Cultural Foundation to IJ. LUV is funded by the Helsinki University Research Foundation and the Paulo Foundation. VJV is funded by the National Institutes of Health (grant R01 MH086117 and U24 MH068457). This work was also supported in part by an allocation of computing time from the Ohio Supercomputer Center Grant PCCR0002 to VJV.

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Oikkonen, J., Huang, Y., Onkamo, P. et al. A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions. Mol Psychiatry 20, 275–282 (2015). https://doi.org/10.1038/mp.2014.8

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