UCSF

Absolute pitch (AP), also known as perfect pitch, is a rare pitch-naming ability with unknown etiology. Some scientists maintain that its manifestation depends solely on environmental factors, while others suggest that genetic factors contribute to it. We hypothesized that certain genetic variants predispose individuals with sufficient musical training to develop absolute pitch. We sought to identify those variants and to learn more about the etiology of absolute pitch using survey and pitch-naming test data from our participants. Our survey and test data agreed with previous observations that pitch-naming ability correlates with an early age of musical training onset, and the data exhibited the accuracy and precision of pitch-naming by AP possessors. Our AP twin study indicated that genetic factors contribute to absolute pitch's etiology, but our segregation analysis revealed that it was not inherited in a simple Mendelian fashion. After collecting DNA samples from informative individuals, we conducted linkage analyses on multiplex absolute pitch families genotyped with microsatellite and single nucleotide polymorphism (SNP) markers and found a region of significant linkage in families of European descent on chromosome 8q24.21, along with suggestive linkage regions on 7q22.3, 8q21.11, and 9p21.3. There was evidence for genetic heterogeneity both within and between populations of different ancestry. In parallel with the linkage study, we attempted to discover genetic variants that were associated with AP in the Ashkenazi Jewish population using a genome-wide association study, but no variants were conclusively associated with AP. We then searched for AP-predisposing genetic variants by first Sanger sequencing candidate genes in eight AP individuals and subsequently conducting targeted next-generation sequencing to sequence almost all genes in the four candidate linkage regions in ten AP individuals. Although a number of candidate AP-predisposing variants emerged from these data, including many novel SNPs, limited follow-up analysis did not conclusively support the association of the variants with AP. Overall, our study of the genetic epidemiology of absolute pitch indicated that it is a complex trait that is genetically heterogeneous, with environmental, epigenetic, and stochastic factors also perhaps contributing to its genesis.