Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population

Abstract

ABSTRACTBackground Musical abilities such as recognising music and singing performance serve as means for communication and are instruments in sexual selection. Specific regions of the brain have been found to be activated by musical stimuli, but these have rarely been extended to the discovery of genes and molecules associated with musical ability. Methods A total of 1008 individuals from 73 familieswere enrolled and a pitch-production accuracy test wasapplied to determine musical ability. To identify geneticloci and variants that contribute to musical ability, we conducted family-based linkage and association analyses, and incorporated the results with data from exome sequencing and array comparative genomic hybridisationanalyses.Results We found significant evidence of linkage at 4q23 with the nearest marker D4S2986 (LOD=3.1), whose supporting interval overlaps a previous study in Finnish families, and identified an intergenic single nucleotide polymorphism (SNP) (rs1251078, p=8.4×10.17) near UGT8, a gene highly expressed inthe central nervous system and known to act in brain organisation. In addition, a non-synonymous SNP in UGT8 was revealed to be highly associated with musical ability (rs4148254, p=8.0×10.17), and a 6.2 kb copy number loss near UGT8 showed a plausible association withmusical ability (p=2.9×10.6).Conclusions This study provides new insight into the genetics of musical ability, exemplifying a methodologyto assign functional significance to synonymous and noncoding alleles by integrating multiple experimentalmethods.